==================================CMR43================================== 43. Search on recent advances in treatment of non small cell adenocarcinomas of the lung, including monoclonal antibodies, chemotherapy, hyperthermia and radiation, etc. 1 UI - 87116428 AU - Wouters EF ; Oei TK ; Soeters PB ; Havenith MG ; Van Engelshoven JM ; Greve LH TI - The value of computed tomography to the staging of non-small-cell primary bronchogenic carcinoma: a prospective study. AB - The value of computed tomography (CT) for the diagnosis of non-small-cell primary bronchogenic carcinoma with regard to T and N classifications was prospectively evaluated in a series of 29 patients. The sensitivity of CT in evaluating the extension of tumor to pleura or mediastinum was 100%, with only a 76% specificity. Computed tomography demonstrated 73 lymph nodes greater than or equal to 10 mm and 55 lymph nodes less than 10 mm in 27 patients. Invasive staging showed 23 lymph nodes greater than or equal to 10 mm and 22 nodes less than 10 mm which were not visualized by CT. Malignant invasion was found at histology in only one of these lymph nodes. The majority of nodes not visualized by CT were localized in the left paratracheal group, right and left tracheobronchial groups and the aortopulmonary window. MH - Adult ; Aged ; Carcinoma, Bronchogenic/PATHOLOGY/*RADIOGRAPHY ; Carcinoma, Non-Small Cell Lung/PATHOLOGY/*RADIOGRAPHY ; Diagnosis, Differential ; Female ; Human ; Lung Neoplasms/ PATHOLOGY/*RADIOGRAPHY ; Lymph Nodes/PATHOLOGY/*RADIOGRAPHY ; Lymphatic Metastasis ; Male ; Mediastinum ; Middle Age ; Prospective Studies ; Tomography, X-Ray Computed SO - Neth J Surg 1986 Dec;38(6):167-70 2 UI - 87111946 AU - Springall DR ; Ibrahim NB ; Rode J ; Sharpe MS ; Bloom SR ; Polak JM TI - Endocrine differentiation of extra-pulmonary small cell carcinoma demonstrated by immunohistochemistry using antibodies to PGP 9.5, neuron-specific enolase and the C-flanking peptide of human pro-bombesin. AB - Several recent studies have confirmed the endocrine nature of small cell carcinoma of the lung. In extra-pulmonary sites, small cell 'undifferentiated' carcinomas have classical morphological features similar to their pulmonary counterpart. We therefore investigated, using immunocytochemistry, the possibility that the non-pulmonary neoplasms may also be endocrine in nature. Sections of 29 small cell carcinomas from oesophagus, stomach, larynx, colon and urinary bladder were immunostained using antisera to protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), cytokeratin, leucocyte common antigen and peptides including bombesin, the C-flanking peptide of human probombesin, adrenocorticotrophic hormone, neurotensin, calcitonin and pancreatic polypeptide. All the tumours showed immunoreactivity for at least one of the two general endocrine markers PGP 9.5 and NSE. Twenty-three of the 29 cases were immunoreactive for PGP 9.5, 27 for NSE. All were positive for cytokeratin and negative for leucocyte common antigen. Of the regulatory peptides, immunoreactivity was obtained with antisera to bombesin (one case), the C-flanking peptide of human pro-bombesin (14 cases), adrenocorticotrophic hormone (one case) and calcitonin (three cases). No PGP 9.5-, NSE- or peptide-like immunoreactivity was detected in 25 control tumours from similar sites, including lymphomas and poorly differentiated tumours. These results suggest that non-pulmonary small cell carcinoma has an endocrine character. MH - Adrenocorticotropic Hormone/METABOLISM ; Bombesin/*ANALYSIS/ IMMUNOLOGY ; Carcinoma, Oat Cell/*ANALYSIS/PATHOLOGY ; Esophageal Neoplasms/ANALYSIS ; Histocytochemistry ; Human ; Immunoenzyme Technics ; Neuropeptides/*ANALYSIS/IMMUNOLOGY ; Phosphopyruvate Hydratase/*ANALYSIS/IMMUNOLOGY SO - J Pathol 1986 Nov;150(3):151-62 3 UI - 87098693 AU - Focan C ; Le Hung S ; Frere MH ; Schallier D TI - Ambulatory combination chemotherapy with oral etoposide and cisplatin for advanced non small cell lung carcinoma patients. A phase II study. AB - Thirty nine male patients with locally advanced and/or extensive non small cell lung cancer (NSCLC) were treated with oral etoposide (240 mg/m2 days 1 to 3) and cisplatin (100 mg/m2 day 4) according to a fully ambulatory schedule. Eight out of 33 (24%) evaluable patients achieved a partial response (PR) and 6 a minor response (MR). Stable disease (SD) was observed in 7 (25%) and progressive disease (P.D.) in 12 (26%). Median survival time (MST) of all patients was 8 months. No difference in MST was observed between limited (LD) and extensive disease (ED) patients. Only overall responding patients (PR + MR + SD) in the E.D. subgroup lived significantly longer than PD patients. Patients with LD did not obtain a significant survival benefit whether or not a response was achieved. The overall toxic cost of the regimen was low and patient tolerance remarkably good. This combination chemotherapy can safely be recommended for ambulatory use and does not seem to compromise heavily the patients' quality of life. MH - Administration, Oral ; Aged ; Antineoplastic Agents, Combined/ *THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/THERAPEUTIC USE ; Drug Evaluation ; Etoposide/*ADMINISTRATION & DOSAGE/ ADVERSE EFFECTS/THERAPEUTIC USE ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Patient Compliance ; Support, Non-U.S. Gov't SO - Anticancer Res 1986 Sep-Oct;6(5):977-81 4 UI - 87098686 AU - Volm M ; Drings P ; Mattern J ; Sonka J ; Vogt-Moykopf I ; Wayss K TI - Relevance of DNA-fluorimetry and short-term resistance testing for adjuvant treatment of non-small cell lung carcinomas. AB - In a clinical study 127 patients with previously untreated stage III non-small cell lung carcinomas (NSCLC) were investigated using flow cytometry and an in vitro short-term test for predicting resistance to cytostatic agents. Patients with aneuploid tumors and tumors with high proliferative activity had significantly shorter survival times than those with diploid or low proliferating tumors. The aim of this study was to find out whether groups of patients classified according to the additionally observed prognostic factors, experience an advantage or disadvantage from particular modalities of treatment. Seventy-nine patients had surgery alone, 18 patients were treated additionally with chemotherapy, and 30 patients with radiation. Patients with aneuploid, low proliferating and in vitro resistant tumors showed no different survival rates after treatment with chemo- and radiotherapy adjuvant to surgery. In contrast, patients with high proliferating tumors died earlier under adjuvant chemotherapy and radiation. Patients with in vitro chemosensitive tumors had shorter survival times after irradiation than patients who had surgery alone or who were treated with adjuvant chemotherapy. MH - Adult ; Aged ; Carcinoma, Non-Small Cell Lung/*THERAPY ; Carmustine/THERAPEUTIC USE ; Clinical Trials ; Combined Modality Therapy ; Drug Resistance ; DNA/*ANALYSIS ; Female ; Flow Cytometry ; Fluorometry ; Fluorouracil/THERAPEUTIC USE ; Human ; Interphase ; Lung Neoplasms/*THERAPY ; Male ; Middle Age ; Prognosis ; Time Factors SO - Anticancer Res 1986 Sep-Oct;6(5):931-4 5 UI - 87098651 AU - McLean JS ; Frame MC ; Freshney RI ; Vaughan PF ; Mackie AE ; Singer I TI - Phenotypic modification of human glioma and non-small cell lung carcinoma by glucocorticoids and other agents. AB - Glucocorticoids are cytostatic for human glioma grown at a high cell density in cell culture. The effect is not cytotoxic, appears to involve a modification of the cell surface, and has been detected with methyl prednisolone, dexamethasone, and beta-methasone. Glucocorticoids were also found to reduce malignancy-associated properties (plasminogen activator and endothelial mitogenesis) and enhance differentiation (glutamyl synthetase activity and high affinity GABA uptake). Cytostasis was also seen at high cell densities in non-small cell lung carcinoma with a concomitant reduction in plasminogen activator activity and endothelial mitogenesis. Preliminary data on surfactant production in A549 cells suggests that the repression of malignancy-associated properties is accompanied by an increase in cell differentiation. Treatment of the WIL adenocarcinoma gown as a xenograft in nude mice caused total cessation of growth and massive central necrosis in the tumor. MH - Astrocytoma/PATHOLOGY ; Brain Chemistry ; Carcinoma, Non-Small Cell Lung/*PATHOLOGY ; Cell Line ; Dactinomycin/PHARMACODYNAMICS ; Dexamethasone/PHARMACODYNAMICS ; Glioma/*PATHOLOGY ; Glucocorticoids/*PHARMACODYNAMICS ; Glutamine Synthetase/ METABOLISM ; Gonadotropins, Chorionic/PHARMACODYNAMICS ; GABA/ METABOLISM ; Human ; Lung Neoplasms/PATHOLOGY ; Mitosis/DRUG EFFECTS ; Phenotype ; Plasminogen Activators/PHARMACODYNAMICS ; Support, Non-U.S. Gov't ; Tissue Extracts/PHARMACODYNAMICS SO - Anticancer Res 1986 Sep-Oct;6(5):1101-6 6 UI - 87095580 AU - Kasai K ; Kameya T ; Okuda T ; Terasaki PI ; Iwaki Y TI - Immunohistochemical examination of lung cancers using monoclonal antibodies reacting with sialosylated Lewisx and sialosylated Lewisa. AB - In order to explore the relationship between the expression of cancer-associated glycolipids such as sialylated Lex (SLEX) and sialylated Lea (SLEA) and the histological subtypes of lung cancers, 30 cases of small cell carcinoma (SCC) and 47 cases of non-small cell carcinoma (non-SCC) were examined immunohistochemically using monoclonal antibodies reacting with SLEX and SLEA. The forty-seven cases of non-SCC included 20 cases of adenocarcinoma, 20 of squamous cell carcinoma and 7 of large cell carcinoma. Tumour cells of most non-SCCs expressed SLEX and SLEA. In adenocarcinomas, the number of tumour cells having SLEX and SLEA was more than that of squamous cell carcinomas, large cell carcinomas and SCC. In SCC, 14 of the 30 cases were found to be positive for both antigens. Although the cancer cells of 11 cases of 17 intermediate cell type SCC had both antigens, the cells of only 3 of 13 oat cell tumours expressed SLEX and SLEA. The present study shows that SLEX and SLEA are useful markers for lung adenocarcinomas, that most cases of intermediate cell type of SCCs have characteristics similar to non-SCC but that many oat cell tumours lack them. MH - Adenocarcinoma/*IMMUNOLOGY ; Antibodies, Monoclonal/IMMUNOLOGY ; Antigens, Neoplasm/*ANALYSIS ; Carcinoma, Oat Cell/*IMMUNOLOGY ; Fetus ; Glycolipids/*ANALYSIS ; Human ; Immunoenzyme Technics ; Lewis Blood-Group System/*IMMUNOLOGY ; Lung Neoplasms/*IMMUNOLOGY SO - Virchows Arch [A] 1986;410(3):253-61 7 UI - 87086197 AU - Kanzawa F ; Matsushima Y ; Ishihara J ; Shimizu E ; Sasaki Y ; Eguchi K ; Shinkai T ; Saijo N ; Miyazawa N ; Hamburger AW TI - In vitro chemosensitivity patterns of carcinoma of the lung in human tumor clonogenic assay. AB - One hundred and sixty-eight different specimens of human carcinoma of the lung were tested for in vitro drug sensitivity using the human tumor clonogenic assay (HTCA) originally described by Hamburger and Salmon. One hundred and twenty-two (73%) specimens grew adequately for chemosensitivity testing. Most tumors were resistant to chemotherapeutic drugs, but in vitro sensitivity, regardless of the type of drugs, varied markedly from specimen to specimen. Although response rates to individual drugs ranged between 9% and 23%, half the specimens tested were sensitive in vitro to at least one drug. A higher in vitro sensitivity rate was observed in small cell lung carcinoma (31%) than in non-small cell lung carcinoma (17%). The frequency of in vitro sensitivity was greater for patients who had received no prior chemotherapy than those who were in relapse. These in vitro results are similar to current clinical experience. There was a significant association between in vitro sensitivity of cells from a primary tumor as compared to its metastases. Overall HTCA appears to be useful in selecting appropriate chemotherapy for individual patients with carcinoma of the lung. MH - Antineoplastic Agents/*PHARMACODYNAMICS ; *Colony-Forming Units Assay ; Human ; Lung Neoplasms/*DRUG THERAPY/SECONDARY ; Support, Non-U.S. Gov't ; *Tumor Stem Cell Assay SO - J Pharmacobiodyn 1986 Sep;9(9):715-21 8 UI - 87081943 AU - Neal MH ; Kosinski R ; Cohen P ; Orenstein JM TI - Atypical endocrine tumors of the lung: a histologic, ultrastructural, and clinical study of 19 cases. AB - Lung cancers are divided by light microscopic criteria into several categories, but only two categories are recognized clinically--small cell and non-small cell carcinomas. Transmission electron microscopy has revealed unexpected complexity within each category, blurring the distinctions between them. The present study was undertaken to determine the incidence of dense-core, neuroendocrine-type granules in lung tumors diagnosed by light microscopy as non-small cell carcinomas, i.e., atypical endocrine tumors, and the clinical significance of their identification. Of 205 consecutive primary and metastatic lung cancers, 19 (9 per cent) diagnosed as non-small cell carcinomas by light microscopy were seen to contain neuroendocrine-type granules by electron microscopy and thus were reclassified as atypical endocrine tumors of the lung. Staining with silver stains, periodic acid-Schiff (PAS), PAS with diastase digestion, and mucicarmine was positive in 18, 15, 14, and eight of the 19 cases, respectively. Electron microscopy revealed glandular differentiation in 12 cases and tonofilaments in eight cases, although none of the tumors met the criteria for identification as squamous cell carcinomas. Clinically, the cancers appeared to resemble non-small cell carcinoma more closely than small cell carcinoma. Median survival (12 months) and response to combination chemotherapy (22 per cent) were in the range reported for non-small cell carcinoma. There were no complete responses, despite the use in some cases of regimens active against small cell carcinoma. However, one patient, the only one to date so treated, had a dramatic response to streptozotocin/5-fluorouracil, suggesting that, as in metastatic carcinoid, this combination may have value in the treatment of atypical endocrine tumors of the lung. MH - Adenocarcinoma/PATHOLOGY ; Adult ; Aged ; Carcinoma, Non-Small Cell Lung/*PATHOLOGY ; Carcinoma, Oat Cell/PATHOLOGY ; Cytoplasmic Granules/PATHOLOGY ; Female ; Human ; Lung Neoplasms/ *PATHOLOGY/THERAPY/ULTRASTRUCTURE ; Male ; Middle Age ; Retrospective Studies ; Support, Non-U.S. Gov't SO - Hum Pathol 1986 Dec;17(12):1264-77 9 UI - 87078520 AU - Scagliotti GV ; Bardessono F ; Gozzelino F ; D'Apuzzo C ; Albera C ; Pescetti G TI - Combination chemotherapy for non small cell lung cancer stage III M0-1 with cisplatin and vinblastine in a divided-dose schedule. AB - Twenty-nine patients with advanced non small cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin and divided-dose vinblastine. In 27 evaluable patients 15% reached partial response and 59% stable disease. Extension of disease, histological type, performance status and weight loss had no relationship to response. Median duration of response was 10.2 months with a median survival time of 15.4 months in responding patients compared with 14 months of stable disease (p:n.s.) and 4.8 months of progressive disease (p less than 0.001). Gastrointestinal, neurological side effects and the development of a severe debilitation syndrome were the most troublesome toxicities of this treatment. The regimen is not generally suitable for treatment of advanced NSCLC. MH - Adult ; Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/ ADMINISTRATION & DOSAGE ; Creatinine/BLOOD ; Drug Administration Schedule ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Vinblastine/ADMINISTRATION & DOSAGE SO - Chemioterapia 1986 Oct;5(5):351-5 10 UI - 87078067 AU - Bonomi PD ; Pazdur R ; Stolbach L ; Mason B ; Ettinger D TI - Phase II trial of mitomycin, vindesine, and hexamethylmelamine in metastatic non-small cell bronchogenic carcinoma. AB - Mitomycin (10 mg/m2 iv on Day 1), vindesine (3 mg/m2 iv on Days 1 and 8), and hexamethylmelamine (100 mg/m2/day orally on Days 1-14) was administered to 32 patients with metastatic non-small cell bronchogenic carcinoma. No patient had been previously treated with chemotherapy and Eastern Cooperative Oncology Group (ECOG) performance status was 0-1 in 21 of 32 patients. Eleven partial responses (34%) were observed, with a median duration of 9 weeks. No complete responses were observed in this group of patients, whose median survival duration was 22 weeks. Moderate leukopenia (median leukocyte count nadir, 2500/mm3) was the major toxic effect. Although this regimen is active and relatively nontoxic, it will not be utilized in future ECOG trials because it has not produced an apparent improvement in survival duration. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Carcinoma, Bronchogenic/*DRUG THERAPY ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Drug Evaluation ; Female ; Hexamethylmelamine/ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Mitomycins/ ADMINISTRATION & DOSAGE ; Neoplasm Metastasis ; Support, U.S. Gov't, P.H.S. ; Vindesine/ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Dec;70(12):1447-8 11 UI - 86195411 AU - Perez CA ; Bauer M ; Edelstein S ; Gillespie BW ; Birch R TI - Impact of tumor control on survival in carcinoma of the lung treated with irradiation [published erratum appears in Int J Radiat Oncol Biol Phys 1986 Nov;12(11):2057] AB - The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1-3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course (p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000-6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure (p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled (p = 0.001). In patients surviving 12 months after treatment with 5000-6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 29 months, in contrast to 18 months, if they developed intrathoracic failure (p = 0.05). In patients treated with 4000 cGy, the median survival was 23 months with control and 18 months without control of the intrathoracic tumor [corrected] (p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant (p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung.(ABSTRACT TRUNCATED AT 400 WORDS) MH - Carcinoma, Bronchogenic/MORTALITY/PATHOLOGY/*RADIOTHERAPY ; Carcinoma, Oat Cell/MORTALITY/PATHOLOGY/*RADIOTHERAPY ; Clinical Trials ; Human ; Lung Neoplasms/MORTALITY/PATHOLOGY/*RADIOTHERAPY ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Random Allocation SO - Int J Radiat Oncol Biol Phys 1986 Apr;12(4):539-47 12 UI - 87072633 AU - Nonomura A ; Hayashi M ; Watanabe K ; Takayanagi N ; Ohta G TI - Studies on the pathogenesis of hepatocellular carcinoma in HBV-negative alcoholic cirrhotics. AB - Ninety five cases of HBV marker-negative cirrhosis with excess alcohol intake were examined clinicopathologically to obtain some clues and insights into the pathogenesis of hepatocellular carcinoma (HCC). The following data were obtained: cases were divided morphologically into 37 cases of macronodular cirrhosis (MacCir), 16 mixed cirrhosis (MixCir), and 42 micronodular cirrhosis (MicCir), the mean age at death was the oldest in MacCir (61 yrs), the youngest in MicCir (51 yrs), and intermediate in MixCir (59 yrs), association of HCC was common both in MacCir and MixCir (78 and 63%, respectively) but infrequent in MicCir (17%), all livers of MicCir with HCC had broad collapse and a small number of macronodules in non-cancerous areas and the mean age of them was older than that of MicCir without both the collapse and macronodules (56 vs 48 yrs), in total cases, the mean age at death of patients with HCC was 7 years older than that without HCC (60 vs 53 yrs), the mean liver weight was the largest in MicCir (1,211 g), the smallest in MacCir (829 g), and intermediate in MixCir (1,022 g), the incidence of MacCir was significantly higher in patients who had given up alcohol for more than one year before death than those without abstinence, and neither the subtypes of cirrhosis nor the incidence of HCC was significantly related to the total amount of alcohol intake. These data indicate that the development of HCC in HBV-negative alcoholics with cirrhosis occurs in relation to the development of macronodules and loss of liver weight, most likely along with the prolongation of the life span. MH - Adult ; Age Factors ; Aged ; Hepatoma/*ETIOLOGY ; Human ; Liver Cirrhosis, Alcoholic/CLASSIFICATION/*COMPLICATIONS/PATHOLOGY ; Liver Neoplasms/*ETIOLOGY ; Liver/PATHOLOGY ; Middle Age ; Organ Weight SO - Acta Pathol Jpn 1986 Sep;36(9):1297-305 13 UI - 87067038 AU - Schmid KW ; Kr:oll M ; Hofst:adter F ; Ladurner D TI - Small cell carcinoma of the thyroid. A reclassification of cases originally diagnosed as small cell carcinomas of the thyroid. AB - 99 cases of undifferentiated carcinomas of the thyroid and nine cases of primary malignant Non-Hodgkin lymphomas of the thyroid were examined from 1967 to 1983 in our institute. Among the undifferentiated carcinomas nine cases were classified as small cell subtype. Over the years, the histopathological handling in regard to small cell subtype of undifferentiated carcinoma and primary malignant Non-Hodgkin lymphoma has changed. The frequency of primary malignant Non-Hodgkin lymphoma has increased conspicuously in the last few years, whereas the number of small cell carcinomas decreased. A reclassification, based on immunohistochemical investigation for tumor markers of the nine cases originally diagnosed as small cell carcinomas from 1967 to 1983 revealed that five cases were poorly differentiated carcinomas or undifferentiated carcinomas of the spindle cell type. In three cases the primary diagnosis had to be revised into malignant Non-Hodgkin lymphoma of the diffuse "histiocytic: type. The postmortem examination of the patient with the remaining small cell carcinoma "of the thyroid: revealed a clinically undetected small cell carcinoma of the lung with metastases to the cervical lymph nodes and the thyroid gland. These findings are in agreement with the results of several recently published papers indicating that true small cell carcinoma of the thyroid must be a very rare tumor. MH - Adult ; Aged ; Aged, 80 and over ; Calcitonin/ANALYSIS ; Carcinoma, Oat Cell/ANALYSIS/*CLASSIFICATION ; Female ; Histocompatibility Antigens/ANALYSIS ; Human ; Immunoenzyme Technics ; Lymphoma, Non-Hodgkin's/ANALYSIS/*CLASSIFICATION ; Male ; Middle Age ; Peptides/ANALYSIS ; Thyroglobulin/ANALYSIS ; Thyroid Neoplasms/ANALYSIS/*CLASSIFICATION SO - Pathol Res Pract 1986 Oct;181(5):540-3 14 UI - 87063905 AU - Fuks JZ ; Patel H ; Hornedo J ; Van Echo DA ; Moody M ; Aisner J TI - Infections in patients with non-small-cell lung cancer treated with intensive induction chemotherapy. AB - The records of 65 consecutive patients with non-small-cell lung cancer (NSCLC) treated with intensive induction chemotherapy were reviewed to study the infectious complications during therapy and to analyze the relationship of the frequency of infections to various predisposing factors. A total of 44 infectious episodes were observed among 30 of the 65 patients. Of the 44 infections, 18 were microbiologically documented and 19 clinically. Seven (16%) infections were without microbiological or clinical documentation and were categorized as "possible: infections. Among the 18 microbiologically documented infections, fifteen (83%) were caused by bacteria and three by fungi. The most frequent bacteria identified in 11 (61%) of the 18 infections were gram-negative organisms, Escherichia coli and Klebsiella pneumoniae being the most frequent. Eight of the 44 infections were associated with bacteremia and three with microbiologically documented pneumonias. There were three drug-related infectious deaths, two associated with bacteremia and one with possible infections. All 44 infectious episodes presented with WBC counts of less than 1,000/microliter, and 34 (79%) had WBC counts of less than 500/microliter. We observed that during therapy, patients with poor performance status (less than 80%) are at a much higher risk to develop infectious complications than those with good performance status (greater than 80%; p less than .001). Although encouraging responses with intensive chemotherapy have been reported for NSCLC in several studies, a major impact of chemotherapy on the survival of patients with this disease has yet not been established. Thus, intensive chemotherapy for NSCLC should remain an experimental treatment modality and should be offered only to patients with good prognostic factors such as those defined by pretreatment performance status. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Bacterial Infections/*ETIOLOGY ; Candidiasis/ *ETIOLOGY ; Carcinoma, Non-Small Cell Lung/COMPLICATIONS/*DRUG THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE ; Cyclophosphamide/ ADMINISTRATION & DOSAGE ; Doxorubicin/ADMINISTRATION & DOSAGE ; Etoposide/ADMINISTRATION & DOSAGE ; Female ; Human ; Lung Neoplasms/COMPLICATIONS/*DRUG THERAPY ; Male ; Middle Age ; Opportunistic Infections/*ETIOLOGY ; Risk SO - Med Pediatr Oncol 1986;14(5):255-61 15 UI - 87059956 AU - Gandara DR ; DeGregorio MW ; Wold H ; Wilbur BJ ; Kohler M ; Lawrence HJ ; Deisseroth AB ; George CB TI - High-dose cisplatin in hypertonic saline: reduced toxicity of a modified dose schedule and correlation with plasma pharmacokinetics. A Northern California Oncology Group Pilot Study in non-small-cell lung cancer. AB - Although increased efficacy has been described with a five-day schedule of high-dose cisplatin (CDDP) in hypertonic saline, severe myelosuppression and cumulative neurotoxicity have limited the usefulness of this therapy. In order to evaluate a possible dose-response relationship in non-small-cell lung cancer (NSCLC), 17 patients with metastatic disease were treated with a modified dose schedule delivering the same total dose (200 mg/m2) in a divided day 1 and 8 schedule. During a pilot study, a total of 47 cycles of therapy were administered, with a median of three cycles per patient and a median total cumulative dose of 600 mg/m2. Nine of 17 patients received at least 600 mg/m2. While nephrotoxicity was similar to previous reports of the five-day schedule, the incidence and severity of myelosuppression and peripheral neuropathy were markedly reduced. Using this modified schedule, severe myelosuppression did not occur. Clinically severe peripheral neuropathy developed in only one patient (6%). The overall response rate was 47% (eight of 17 patients). Plasma platinum pharmacokinetics during five cycles of the modified day 1 and 8 schedule were compared with pharmacokinetics of the five-day schedule. Accumulation of plasma ultrafiltrate platinum occurred in the five-day schedule, but not in the day 1 and 8 schedule. This difference in pharmacokinetics is one possible explanation for the reduced toxicity of this modified schedule. Although the degree of activity seen in this pilot study is encouraging, the efficacy of high-dose CDDP in NSCLC remains to be defined. In view of reduced myelosuppression and neurotoxicity, further trials with this modified schedule are indicated. MH - Adult ; Aged ; California ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ METABOLISM ; Comparative Study ; Drug Administration Schedule ; Female ; Human ; Kinetics ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Peripheral Nerve Diseases/CHEMICALLY INDUCED ; Pilot Projects ; Platinum/BLOOD ; Saline Solution, Hypertonic ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - J Clin Oncol 1986 Dec;4(12):1787-93 16 UI - 87059955 AU - Klastersky J ; Sculier JP ; Ravez P ; Libert P ; Michel J ; Vandermoten G ; Rocmans P ; Bonduelle Y ; Mairesse M ; Michiels T ; et al TI - A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma. AB - We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival. MH - Actuarial Analysis ; Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/*THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY/MORTALITY ; Cisplatin/ADMINISTRATION & DOSAGE ; Drug Evaluation ; Etoposide/ADMINISTRATION & DOSAGE ; Female ; Hematologic Diseases/CHEMICALLY INDUCED ; Human ; Lung Neoplasms/*DRUG THERAPY/MORTALITY ; Male ; Middle Age ; Prognosis ; Random Allocation SO - J Clin Oncol 1986 Dec;4(12):1780-6 17 UI - 87051358 AU - Endo K ; Kamma H ; Ogata T TI - Two murine monoclonal antibodies against human lung cancer-associated antigens. AB - Two murine monoclonal antibodies, MAb 8 (immunoglobulin G3 kappa) and MAb 15 (immunoglobulin G1 kappa), were produced after immunization with TKB-2, a variant cell line of human small cell carcinoma of the lung. In enzyme-linked immunosorbent assay, these antibodies reacted with four major types of lung cancer cell lines and various extrapulmonary tumor cell lines. Immunohistological study, however, showed highly specific binding to lung cancers; MAb 8 bound to 68% of 65 lung cancers, and MAb 15 bound to 72% of them. Interestingly, both antibodies were more reactive with non-small cell than small cell lung cancers and bound most frequently to large cell carcinoma. Most extrapulmonary tumor tissues were negative in staining with a few exceptions; endodermal sinus tumor (two of two) was positive to both antibodies, breast carcinoma (one of five) to MAb 8, gastric carcinoma (one of three), and malignant melanoma (one of one) to MAb 15. Cross-reactions with normal tissues were limited; MAb 8 reacted with adult and fetal lung, and MAb 15 with esophagus and renal tubules. MAb 8 recognized a Mr 48,000 glycoprotein antigen (carbohydrates as its epitope), and MAb 15 recognized two proteins (Mr 85,000 and 45,000) (peptides as their epitopes). These two antibodies, detecting novel antigens extensively associated with and highly specific to lung cancers, are potentially useful for the study of lung cancer. MH - Animal ; Antibodies, Monoclonal/*IMMUNOLOGY ; Antigenic Determinants/ANALYSIS ; Antigens, Neoplasm/*ANALYSIS/IMMUNOLOGY ; Cell Line ; Female ; Human ; Lung Neoplasms/*IMMUNOLOGY ; Mice ; Mice, Inbred BALB C ; Molecular Weight ; Support, Non-U.S. Gov't SO - Cancer Res 1986 Dec;46(12 Pt 1):6369-73 18 UI - 87049495 AU - Mackillop WJ ; Ward GK ; O'Sullivan B TI - The use of expert surrogates to evaluate clinical trials in non-small cell lung cancer. AB - One hundred and eighteen doctors who treat pulmonary neoplasms in Ontario were asked how they would wish to be treated if they had non-small cell lung cancer. Four different scenarios were given. The physicians were then asked if they would consent to take part as subjects in one or more clinical trials for which they would be eligible in those situations. The proportion of respondents who would consent to each study ranged from 11% to 64%. Reasons given for refusing to participate as subjects in each trial were varied, but many felt that the trials offered unacceptable options for treatment. Medical oncologists consented to each study more frequently than radiation oncologists, respirologists or thoracic surgeons but all disciplines ranked the 6 studies in the same order of acceptability. It is concluded that some patients with non-oat cell lung cancer currently receive experimental therapies with high risk/benefits ratios which experts in the field would not accept for themselves. It is suggested that the expert surrogate system may be useful as an adjunct to the institutional review board in evaluating new trials before they are activated. MH - *Attitude of Health Personnel ; Carcinoma, Non-Small Cell Lung/ *THERAPY ; *Clinical Trials ; Human ; Informed Consent ; Lung Neoplasms/*THERAPY ; Random Allocation ; Support, Non-U.S. Gov't SO - Br J Cancer 1986 Oct;54(4):661-7 19 UI - 87049484 AU - Simmonds AP ; Hamilton PS ; Kerr H ; Harvey K ; Moyes P ; Davidson KG ; Faichney A TI - Drug sensitivity of non small cell carcinoma of lung by clonogenic assay in several media. AB - Lung tumours of non small cell pathology were cultured by clonogenic assay in several media. Culture was successful in spleen conditioned medium, but only 57% grew and low plating efficiencies (PE) meant that only 23% of the original number produced significant drug results. Comparison of rat erythrocyte lysate (REL) medium with serum free defined medium (HITES) and HITES + 10% FBS demonstrated clear enhancement of PE in REL although growth was 100% successful in all these media. Ninety-three percent of samples tested against drugs in REL produced significant results. A later comparison of REL with McCoy's 5A + rbc +/- hydrocortisone produced relatively poor culture success for these 3 media and equivocal growth patterns. Low PE was attributed to age of rats used for rbc. Vindesine and cis-platinum cytotoxicity in spleen conditioned medium were 61% and 15% sensitivity respectively. These do not concur with clinical experience but the figures for overt resistance, at 39% and 69%, correspond with expected non-responders to these regimes. Drug testing in REL produced figures correlating more closely with clinical performance at 45% sensitivity to platinum and 36% of patients sensitive to both drugs, but the vindesine sensitivity at 55% is again discrepant with performance of this drug as a single agent. MH - Carcinoma, Non-Small Cell Lung/*PATHOLOGY ; Cell Survival/DRUG EFFECTS ; Cells, Cultured ; Cisplatin/PHARMACODYNAMICS/ THERAPEUTIC USE ; *Colony-Forming Units Assay ; *Culture Media ; Human ; Lung Neoplasms/DRUG THERAPY/*PATHOLOGY ; *Tumor Stem Cell Assay ; Vindesine/PHARMACODYNAMICS/THERAPEUTIC USE SO - Br J Cancer 1986 Oct;54(4):587-94 20 UI - 87037748 AU - Tong AW ; Lee JC ; Stone MJ TI - Discrimination of human small cell and non-small cell lung tumors by a panel of monoclonal antibodies. AB - The immunohistochemical reactivity of biopsy specimens from different human lung tumor cell types was examined with 4 human small cell lung carcinoma (SCLC)-reactive monoclonal antibodies (MoAbs) (SCLC 1096, SCLC 2051, SCLC 3121, and SCLC 5023) generated in this laboratory, with the use of Formalin-fixed, paraffin-embedded tissue sections. Each MoAb reacted preferentially with SCLC tumors (62-97% of 29 cases tested), with low-to-moderate cross-reactivity with non-SCLC tumors (SCLC 1096, 13.7%; SCLC 2051 and SCLC 3121, 9.8% each; SCLC 5023, 41%, of 51 cases tested). None of the 4 MoAbs reacted with nonmalignant lung biopsy specimens. SCLC tumors were characterized by their collective immunoperoxidase reactivity with the MoAb panel of SCLC 2051, SCLC 3121, and SCLC 5023. Based on unequivocal positive reactions with at least 2 of the 3 MoAbs, this MoAb panel correctly identified 97% (28/29) of SCLC cases of 80 lung tumor cases tested. By contrast, only 4 of 51 (7.8%) non-SCLC cases were positive by the same criterion. These observations suggest that immunohistochemical analysis with these SCLC-reactive MoAbs could help in discriminating small cell from other human lung carcinoma cell types. MH - Antibodies, Monoclonal/*DIAGNOSTIC USE ; Antibodies, Neoplasm/ IMMUNOLOGY ; Antibody Specificity ; Antigens, Neoplasm/IMMUNOLOGY ; Carcinoma, Non-Small Cell Lung/*DIAGNOSIS/IMMUNOLOGY ; Carcinoma, Oat Cell/*DIAGNOSIS/IMMUNOLOGY ; Cell Line ; Human ; Immunochemistry ; Immunoenzyme Technics ; Lung Neoplasms/ *DIAGNOSIS/IMMUNOLOGY ; Support, Non-U.S. Gov't SO - JNCI 1986 Nov;77(5):1023-33 21 UI - 87035759 AU - Mulshine JL ; Glatstein E ; Ruckdeschel JC TI - Treatment of non-small-cell lung cancer. AB - The treatment of non-small-cell lung cancer (NSCLC; including squamous, large-cell anaplastic, and adenocarcinoma) is one of the most frustrating areas in oncology. With the exception of the high cure rates for surgical treatment of truly localized disease, the prognosis for patients with NSCLC is grim. Often rancorous debate has ensued about the best means of exploiting the currently available modalities of radiation therapy and chemotherapy. Recognizing that the effectiveness of the current therapeutic modalities is limited, we will review the treatment results from the past few years that help define where specific treatment options should be used or suggest areas in which to focus future trials. We will also review the implications of current findings in the cell biology of lung cancer as they pertain to the therapy of NSCLC. MH - Antibodies, Monoclonal/DIAGNOSTIC USE/THERAPEUTIC USE ; Antineoplastic Agents/THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/PATHOLOGY/RADIOTHERAPY/*THERAPY ; Clinical Trials ; Combined Modality Therapy ; Human ; Immunotherapy ; Lung Neoplasms/ PATHOLOGY/RADIOTHERAPY/*THERAPY ; Medical Oncology/TRENDS ; Neoplasm Staging ; Palliative Treatment ; Prognosis ; Review SO - J Clin Oncol 1986 Nov;4(11):1704-15 22 UI - 87035745 AU - O'Connell JP ; Kris MG ; Gralla RJ ; Groshen S ; Trust A ; Fiore JJ ; Kelsen DP ; Heelan RT ; Golbey RB TI - Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. AB - To determine the frequency and prognostic importance of pretreatment clinical characteristics in patients currently undergoing treatment for stage III non-small-cell lung cancer (NSCLC), data were collected on 378 patients receiving high-dose (120 mg/m2) cisplatin plus vinca alkaloid combination chemotherapy regimens since 1978. Variables analyzed included age, sex, weight loss, performance status, histologic subtype, presence of extrathoracic metastases, number of metastatic organ sites, presence of liver, bone, or brain involvement, prior radiation or surgery, and serum lactate dehydrogenase (LDH). The effect of a major response to chemotherapy on survival was also investigated. Using multivariable analyses, the following were found to be associated with outcome: initial performance status, with patients having a performance status of 80% to 100% having an increased major objective response rate and survival; bone metastases, which were adversely predictive of response rate and survival; elevated serum LDH and male sex, both of which were associated with shortened survival and remission duration; and the presence of two or more extrathoracic metastatic organ sites, which was associated with shorter survival. When major objective response with chemotherapy was included in a conditional multivariable analysis, it was strongly associated with longer median survival. Information from this analysis may be useful when comparing the response data of completed studies in similar patients, in designing future trials, and in the selection of cisplatin plus vinca alkaloid therapy for individual patients with advanced NSCLC. MH - Adult ; Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY/MORTALITY/PATHOLOGY ; Data Collection ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY/ MORTALITY/PATHOLOGY ; Male ; Middle Age ; Neoplasm Metastasis ; Prognosis ; Statistics ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - J Clin Oncol 1986 Nov;4(11):1604-14 23 UI - 87029805 AU - Kyrkou KA ; Iatridis SG ; Athanassiadou PP ; Lambropoulou S ; Liossi A TI - Immunodetection of neuron-specific enolase and keratin in cytological preparations as an aid in the differential diagnosis of lung cancer. AB - The results of neuron-specific enolase (NSE) and keratin immunodetection in cytological specimens of sputum secured from 41 patients with lung cancer are presented. All 19 cases of small-cell carcinoma showed intense immunoreactivity for NSE. No such immunoreactivity was found in 21 of 22 cases of non-small-cell carcinoma. The single positive result was from a case of large-cell undifferentiated carcinoma. All 10 cases of squamous-cell carcinoma showed immunoreactivity for keratin. The 19 cases of small-cell carcinoma showed no such reactivity. Our findings indicate that immunostaining for NSE and keratin is a valuable aid when a definite diagnosis of small-cell carcinoma of the lung can not be made on the basis of conventional cytologic features. MH - Adenocarcinoma/DIAGNOSIS ; Carcinoma, Oat Cell/*DIAGNOSIS ; Carcinoma, Squamous Cell/DIAGNOSIS ; Diagnosis, Differential ; Enzyme Tests ; Histocytochemistry ; Human ; Immunoenzyme Technics ; Keratin/*ANALYSIS/DIAGNOSTIC USE/IMMUNOLOGY ; Lung Neoplasms/ ANALYSIS/*DIAGNOSIS/ENZYMOLOGY ; Phosphopyruvate Hydratase/ *ANALYSIS/DIAGNOSTIC USE/IMMUNOLOGY ; Sputum/ANALYSIS SO - Diagn Cytopathol 1986 Sep;2(3):217-20 24 UI - 87028345 AU - Lelli G ; Casadio M ; Giuliotti C ; Giordani S ; Martoni A ; Strocchi E ; Pannuti F TI - Phase II studies on weekly cisplatinum plus epirubicin or etoposide in the treatment of advanced non-small cell bronchogenic carcinoma. AB - Thirty-six patients with advanced non-small cell bronchogenic carcinoma were divided in 2 groups for treatment with two different platinum-based combination therapy regimens. All 16 patients who received the weekly administered combination of 10 mg/m2 cisplatin (CDDP) plus 10 mg/m2 epirubicin (4EPIDX) experienced no clinical response. Among the 20 patients who received the combination CDDP (10 mg/m2) plus etoposide (VP16, 60 mg/m2) weekly, 4 of them (20%) showed partial remission (PR). The side effects of both combinations were of mild grade. Further study is needed to verify the effectiveness of the weekly combination of CDDP and VP16 by comparing the above regimen with the "standard: intermittent doses. MH - Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Bronchogenic/*DRUG THERAPY ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Comparative Study ; Doxorubicin/ADMINISTRATION & DOSAGE/ ADVERSE EFFECTS ; Drug Administration Schedule ; Drug Evaluation ; Etoposide/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age SO - Chemioterapia 1986 Aug;5(4):228-31 25 UI - 87028101 TI - Intrapleural and intravenous Corynebacterium parvum in patients with resected stage I and II non-small cell carcinoma of the lung. The Ludwig Lung Cancer Study Group. AB - A prospective randomized trial compared the administration of intrapleural plus intravenous Corynebacterium parvum (C. parvum) versus placebo in patients with resected Stage I and Stage II non-small cell bronchogenic carcinoma. Treatment consisted of 7 mg C. parvum injected into the pleural space and 7 mg C. parvum intravenously once between days 6 and 12 postoperatively and 7 mg intravenously every 3rd month during the 1st year. Intrapleural administration of 35 cc of saline served as the placebo and the flush after intrapleural C. parvum. Of the 303 patients entered into this study, 286 were evaluable, with an average follow-up time of 3.5 years. More complications, especially fever, were observed in patients receiving C. parvum. A fever greater than 38 degrees C was observed in 9% of the patients assigned to placebo and 76% of the patients assigned to C. parvum. There was no significant difference between the treatments with respect to disease-free interval or survival. MH - Aged ; Bacterial Vaccines/ADMINISTRATION & DOSAGE/*THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*SURGERY/THERAPY ; Clinical Trials ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/*SURGERY/THERAPY ; Male ; Middle Age ; Neoplasm Staging ; Propionibacterium acnes/*IMMUNOLOGY ; Random Allocation SO - Cancer Immunol Immunother 1986;23(1):1-4 26 UI - 87028039 AU - Maroun JA ; Maksymiuk A ; Eisenhauer E ; Stewart DJ ; Young V ; Pater J TI - Phase II study of acivicin in non-small cell lung cancer: a National Cancer Institute of Canada Study. AB - Thirty-six previously untreated patients with metastatic non-small cell lung cancer received acivicin at a starting dose of 15 mg/m2, given over 5 days and repeated every 21 days. Hematological toxicity was dose-related; one patient died of neutropenic sepsis at 18 mg/m2. Nonhematological toxicity was mild, with gastrointestinal symptoms being the most prominent. Neurological toxicity was seen in 48% of the patients and consisted of confusion, hallucinations, and sleeping difficulty. A minority of patients required dose reduction because of these symptoms. In 33 evaluable patients, two partial remissions were documented, with seven additional patients showing evidence of minor responses. Although modest, these responses warrant further study of acivicin in non-small cell lung cancer in combination with other agents. MH - Adult ; Aged ; Antibiotics, Antineoplastic/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Canada ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cognition Disorders/CHEMICALLY INDUCED ; Drug Evaluation ; Female ; Hematologic Diseases/CHEMICALLY INDUCED ; Human ; Isoxazoles/ADVERSE EFFECTS/*THERAPEUTIC USE ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Oxazoles/ *THERAPEUTIC USE SO - Cancer Treat Rep 1986 Nov;70(11):1327-8 27 UI - 87027946 TI - Immunostimulation with intrapleural BCG as adjuvant therapy in resected non-small cell lung cancer. The Ludwig Lung Cancer Study Group (LLCSG). AB - A prospective randomized trial was performed to evaluate the role of adjuvant local immunostimulation with bacillus Calmette-Gu:erin (BCG) in resected Stage I and Stage II non-small cell bronchogenic carcinoma. The patients were stratified according to extent of resection and surgical stage, and randomized to treatment or placebo. Adjuvant treatment consisted of a single dose of BCG (Tice) injected into the pleural space between days 6 and 12 postoperatively. Isoniazid was given by mouth for 12 weeks. In the control group saline was injected intrapleurally. Of 441 patients included in the study, 407 were evaluable, 198 of them in the BCG group and 209 in the control group. The average follow-up was 4.7 years. A high rate of complications was noted in the BCG group; after pneumonectomy 22% of these patients developed pleural empyema necessitating further surgical procedures, in comparison with 3% in the placebo group. There was no significant difference between the two randomized groups with respect to survival. There was, however, a significant decrease in the disease-free interval in patients who received BCG (P = 0.044). This detrimental effect with BCG was especially pronounced in pneumonectomized patients (P = 0.028). There was no significant difference between treatment and placebo in patients with lobectomies. Because of no proved benefit of regional administration of BCG (and even of detrimental effects after pneumonectomy) and a high rate of severe complications, the authors advise against the use of BCG intrapleurally as local adjuvant immunostimulation. MH - Aged ; BCG Vaccine/*ADMINISTRATION & DOSAGE ; Carcinoma, Non-Small Cell Lung/*SURGERY/THERAPY ; Clinical Trials ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/*SURGERY/ THERAPY ; Male ; Middle Age ; Neoplasm Recurrence, Local ; Pleura ; Pneumonectomy/ADVERSE EFFECTS ; Prospective Studies ; Pulmonary Embolism/ETIOLOGY ; Random Allocation ; Statistics SO - Cancer 1986 Dec 1;58(11):2411-6 28 UI - 87024144 AU - Sobol RE ; O'Connor DT ; Addison J ; Suchocki K ; Royston I ; Deftos LJ TI - Elevated serum chromogranin A concentrations in small-cell lung carcinoma. AB - Serum chromogranin A concentrations measured by radioimmunoassay in patients with small-cell lung carcinoma were compared with values from healthy adults and patients with non-small-cell lung carcinoma or chronic obstructive pulmonary disease. The mean (+/- SE) level was significantly higher (p less than or equal to 0.02) in patients with small-cell lung carcinoma (815 +/- 290 ng/mL, n = 46) than in normal controls (123 +/- 6 ng/mL, n = 20) or patients with chronic obstructive pulmonary disease (169 +/- 18 ng/mL, n = 39), lung adenocarcinoma (180 +/- 22, ng/mL, n = 62), large-cell lung carcinoma (183 +/- 23 ng/mL, n = 18), or lung epidermoid carcinoma (203 +/- 37 ng/mL, n = 78). The mean concentration in extensive-stage small-cell lung carcinoma (1155 +/- 449 ng/mL, n = 29) was significantly greater (p = 0.026) than in limited disease (234 +/- 56 ng/mL, n = 17). Elevated serum chromogranin A values were seen in 53% of patients with limited and 72% with extensive disease. Four patients originally classified as having non-small-cell lung carcinomas with raised chromogranin A levels were subsequently found to have mixed small-cell and non-small-cell tumors. Serum chromogranin A concentrations may be a useful marker of small-cell lung carcinoma disease activity. MH - Adult ; Carcinoma, Non-Small Cell Lung/BLOOD ; Carcinoma, Oat Cell/*BLOOD ; Chromogranins/*BLOOD ; Human ; Lung Diseases, Obstructive/BLOOD ; Lung Neoplasms/*BLOOD ; Nerve Tissue Proteins/ *BLOOD ; Radioimmunoassay ; Reference Values ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Ann Intern Med 1986 Nov;105(5):698-700 29 UI - 87020271 AU - Paccagnella A ; Brandes A ; Pappagallo GL ; Simioni G ; Fosser VP ; Vinante O ; Salvagno L ; De Besi P ; Chiarion Sileni V ; Fornasiero A ; et al TI - Cisplatin plus vindesine versus cisplatin plus VP16 versus doxorubicin plus cytoxan in non-small-cell carcinoma of the lung. A randomized study. AB - From March 1981 to January 1984, 116 patients with advanced non-small-cell carcinoma of the lung (NSCCL) were randomly assigned to 3 combinations as follows: CDDP + DVA, CDDP + VP16 and DXR + CTX. 94 patients were evaluable for response, 106 for toxicity and survival. Of 31 patients, 15 (48%; 3 CRs and 12 PRs) responded to CDDP + DVA; of 33 patients, 12 (36%, 2 CRs and 10 PRs) responded to CDDP + VP16; of 30 patients, 3 (10%) obtained a PR with DXR + CTX (CDDP + DVA vs DXR + CTX, P less than 0.005; CDDP + VP16 vs DXR + CTX, P less than 0.05; CDDP + DVA vs CDDP + VP16, P = NS). The median duration of response was 22 weeks in the CDDP-DVA group, 17 weeks in the CDDP-VP16 group, and 16 weeks in the DXR + CTX group. No significant difference in survival was observed among the 3 groups (median: 43, 47, 41 weeks, respectively). Hematologic and neurologic toxicities were significantly higher in the DVA-containing regimen. Despite the lack of improvement of overall survival with the CDDP-containing combinations over the DXR + CTX control group, the good response rate makes them suitable to be used in combined therapeutic strategies. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY/ MORTALITY ; Cisplatin/ADMINISTRATION & DOSAGE ; Clinical Trials ; Comparative Study ; Cyclophosphamide/ADMINISTRATION & DOSAGE ; Doxorubicin/ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/ *DRUG THERAPY/MORTALITY ; Middle Age ; Podophyllotoxin/ ADMINISTRATION & DOSAGE ; Random Allocation ; Vindesine/ ADMINISTRATION & DOSAGE SO - Tumori 1986 Aug 31;72(4):417-25 30 UI - 87019399 AU - Little AG ; DeMeester TR ; Ferguson MK ; Skinner DB ; Hoffman PC ; Skosey C ; Blough RR ; Golomb HM TI - Modified stage I (T1N0M0, T2N0M0), nonsmall cell lung cancer: treatment results, recurrence patterns, and adjuvant immunotherapy. AB - We analyzed 96 patients who had surgery with T1N0M0 or T2N0M0 nonsmall cell lung cancer (NSCLC) to identify survival rates and recurrence patterns in well-staged patients and to evaluate adjuvant therapy. Preoperative staging included chest x-ray, gallium 67 scanning, and bronchoscopy in all patients. At thoracotomy, multiple mediastinal lymph node sites were routinely sampled. The results included an operative mortality rate of 5.2%, and the actuarial 5-year survival rate of all patients was 70.0%. Survival of T1N0 (n = 44) and T2N0 (n = 47) patients was 72.1% and 68.3%, respectively (p = NS). Survival was not affected by type of surgery, cell type, sex, age, or race. Late death was due to recurrence in 12 patients, a new airway malignancy in three, and a noncancer problem in six. Disease recurred in 15 patients: four (9.1%) T1N0 patients versus 11 (23.4%) T2N0 patients, p less than 0.05. Recurrence was local in four patients and distant in 11. Second lung cancers developed in six patients at a mean interval of 65.7 months after resection. A prospective, randomized trial of systemic immunotherapy with bacillus Calmette-Guerin (BCG) skin scarification was carried out in 29 patients. Survival in those patients receiving BCG was 85.9% compared with 63.9% for control subjects (p = 0.075) and 69.6% for patients not in the study (p = 0.077). The following conclusions can be made: Resection for well-staged, modified stage I NSCLC results in a 5-year survival rate of 70%. Nearly half the deaths are unrelated to recurrence of the original cancer. Recurrences are more frequent in T2N0 patients, but there is no survival difference compared with T1N0 patients. Systemic recurrences are more frequent than local recurrences, and there is an appreciable incidence of second lung cancers. Adjuvant chemotherapy or radiation therapy does not seem justified, but systemic immunotherapy holds sufficient promise to warrant further investigation. MH - Adult ; Aged ; Aged, 80 and over ; BCG Vaccine/THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/MORTALITY/SECONDARY/*SURGERY ; Combined Modality Therapy ; Female ; Human ; *Immunotherapy ; Lung Neoplasms/MORTALITY/PATHOLOGY/*SURGERY ; Male ; Middle Age ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prospective Studies SO - Surgery 1986 Oct;100(4):621-8 31 UI - 87018901 AU - Splinter T ; Kok T ; Kho S ; Lameris H ; ten Kate F ; Dalesio O ; Dolman B ; Palmen F ; Bouvy J ; Burghouts J ; et al TI - A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer. AB - Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease. MH - Administration, Oral ; Antineoplastic Agents, Combined/ *THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE ; Drug Evaluation ; Etoposide/ ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/*DRUG THERAPY ; Prognosis ; Remission Induction SO - Semin Oncol 1986 Sep;13(3 Suppl 3):97-103 32 UI - 87018900 AU - Greco FA TI - Rationale for chemotherapy for patients with advanced non-small-cell lung cancer. AB - Patients with advanced non-small-cell lung cancer (NSCLC) are difficult to treat effectively. There is a strong rationale to continue clinical investigation, since this approach has been useful for other groups of patients with "resistant: tumors. This report reviews the major reasons to consider chemotherapy in these patients, and discusses several other important auxiliary issues. MH - Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Case Report ; Clinical Trials ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Palliative Treatment SO - Semin Oncol 1986 Sep;13(3 Suppl 3):92-6 33 UI - 87018886 AU - Osoba D ; Rusthoven JJ ; Evans WK ; Turnbull KA TI - Combined chemotherapy and radiation therapy for non-small-cell lung cancer. AB - In a previous study of patients with recurrent or disseminated non-small-cell lung cancer (NSCLC), the combination of bleomycin, etoposide, and cisplatin (BEP) produced objective responses in ten of 17 (59%) patients with large-cell anaplastic carcinoma and in 14 of 35 (40%) with squamous-cell carcinoma. These results prompted a pilot study of combined modality therapy in which two cycles of BEP were administered prior to split-course radiation therapy. Thirty patients with surgically unresectable stage II or III squamous- or large-cell cancer, were entered into the study, of whom 25 were evaluable for response to chemotherapy. One patient (4%) had a complete response (CR), ten (40%) with measureable disease had a partial response (PR), and four (16%) with evaluable disease had significant disease regression prior to radiotherapy (overall response rate, 60%). After radiotherapy, six of 22 (27%) evaluable patients achieved a CR, and six (27%) a PR, for an overall response rate of 55%. Symptom control was achieved with chemotherapy in the majority of patients. The median survival time after the initiation of BEP had not been reached at 52 weeks. The results of this pilot study suggest that a phase III study comparing BEP plus radiation therapy with radiation therapy alone should be undertaken in this subgroup of patients with NSCLC. MH - Antineoplastic Agents, Combined/ADVERSE EFFECTS/*THERAPEUTIC USE ; Bleomycins/ADMINISTRATION & DOSAGE ; Carcinoma, Non-Small Cell Lung/DRUG THERAPY/RADIOTHERAPY/*THERAPY ; Cisplatin/ ADMINISTRATION & DOSAGE ; Combined Modality Therapy ; Etoposide/ ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/DRUG THERAPY/ RADIOTHERAPY/*THERAPY ; Pilot Projects SO - Semin Oncol 1986 Sep;13(3 Suppl 3):121-4 34 UI - 87018885 AU - Bonomi P ; Rowland K ; Taylor SG 4th ; Reddy S ; Lee MS ; Faber LP ; Warren W TI - Phase II trial of etoposide, cisplatin, continuous infusion 5-fluorouracyil, and simultaneous split-course radiation therapy in stage III non-small-cell bronchogenic carcinoma. AB - Survival in patients with locally advanced, non-small-cell lung cancer (NSCLC) is relatively short, despite treatment with surgery or radiation. A phase II study of simultaneous continuous infusion 5-fluorouracil and split-course radiation with or without surgery has shown possible improvement in median survival compared with that observed in trials of radiation alone. Past success with etoposide plus cisplatin in NSCLC has led to the addition of etoposide to the 5-fluorouracil plus cisplatin plus radiation combination. Twenty-four stage III NSCLC patients were treated with this three-drug regimen, and a 74% clinical partial remission rate was observed. Thoracotomy was done in eight of these patients; subsequent histologic examination of the resected specimen revealed no residual tumor in four patients (50%) and only microscopic foci of tumor in two patients (25%). Major toxicities were leukopenia, nausea, and vomiting. Median leukocyte nadir was 2,900/mm3. A leukocyte count less than 1,000/mm3 was observed in two of 24 patients (8%), one of whom expired from progressive pneumonia. All patients experienced nausea and vomiting, which were classified as moderate in three patients (12%) and severe in four (16%). Moderate to severe esophagitis, dermatitis, and pneumonitis were not observed. Median progression-free interval and median survival were not reached after a median follow-up of 163 days. MH - Antineoplastic Agents, Combined/ADVERSE EFFECTS/*THERAPEUTIC USE ; Carcinoma, Bronchogenic/DRUG THERAPY/RADIOTHERAPY/*THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE ; Combined Modality Therapy ; Drug Administration Schedule ; Drug Evaluation ; Etoposide/ ADMINISTRATION & DOSAGE ; Fluorouracil/ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/DRUG THERAPY/RADIOTHERAPY/*THERAPY ; Radiotherapy/ADVERSE EFFECTS SO - Semin Oncol 1986 Sep;13(3 Suppl 3):115-20 35 UI - 87007947 AU - Shinkai T ; Saijo N ; Eguchi K ; Sasaki Y ; Tominaga K ; Sakurai M ; Suga J ; Miyaoka H ; Sano T ; Keicho N ; et al TI - Cisplatin and vindesine combination chemotherapy for non-small cell lung cancer: a randomized trial comparing two dosages of cisplatin. AB - Forty-five patients with advanced non-small cell lung cancer were randomly allocated to receive vindesine (3 mg/m2 every week) plus either high-dose cisplatin (120 mg/m2 every 4 weeks) or low-dose cisplatin (80 mg/m2 every 3 weeks). All patients were previously untreated. The response rate for the high-dose regimen of cisplatin was 39% (9/23) and that for the low-dose regimen of cisplatin was 33% (7/21); the difference was not statistically significant. Only one patient treated with high-dose cisplatin achieved complete response, lasting 6.5 months. The median duration of response was 5.6 months (range, 2.7-7.7) in the high-dose cisplatin group and 6.8 months (range, 1.9-8.9) in the low-dose cisplatin group. The median survival times for the 23 patients treated with the high-dose regimen of cisplatin and for the 21 patients treated with the low-dose regimen of cisplatin were 9.0 and 10.8 months, respectively. Significantly more azotemia occurred in the high-dose cisplatin group than in the low-dose cisplatin group (P less than 0.05). Combination chemotherapy with cisplatin and vindesine showed significant antitumor activity in patients with non-small cell lung cancer. However, the high-dose regimen of cisplatin did not result in a significantly better response rate or survival advantage, and was associated with greater toxicity. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*DRUG THERAPY ; Cisplatin/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Clinical Trials ; Comparative Study ; Female ; Human ; Leukopenia/ CHEMICALLY INDUCED ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Random Allocation ; Support, Non-U.S. Gov't ; Thrombocytopenia/CHEMICALLY INDUCED ; Uremia/CHEMICALLY INDUCED ; Vindesine/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS SO - Jpn J Cancer Res 1986 Aug;77(8):782-9 36 UI - 87007765 AU - Cox JD ; Barber-Derus S ; Hartz AJ ; Fischer M ; Byhardt RW ; Komaki R ; Wilson JF ; Greenberg M TI - Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung? AB - Radiation therapy is widely considered the primary treatment for inoperable "non-small: cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung. MH - Adenocarcinoma/*RADIOTHERAPY ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small Cell Lung/*RADIOTHERAPY ; Carcinoma, Squamous Cell/RADIOTHERAPY ; Comparative Study ; Female ; Human ; Lung Neoplasms/*RADIOTHERAPY ; Male ; Middle Age ; Prognosis ; Retrospective Studies SO - Int J Radiat Oncol Biol Phys 1986 Oct;12(10):1801-5 37 UI - 87006154 AU - Sakamoto Y ; Kamada M ; Irahara M ; Hasebe H ; Daitoh T ; Furumoto H ; Kishi Y ; Mori T TI - Differences in clinical significance of blood group antigens A, B, and H in carcinoma tissue in the uterine cervix. AB - The losses of blood group antigens A, B, and H in carcinoma tissue of the uterine cervix were studied by the avidin-biotin-peroxidase complex (ABC) method and the relations of these losses to invasion and dedifferentiation of primary cancer were examined. The incidence of cases showing complete loss of A or B antigen increased in proportion to the progression of cancer, but in most cases even of invasive cancer, H antigen, the precursor of A and B antigens, was detected. Complete loss of H antigen was not demonstrated in well-differentiated keratinizing invasive carcinomas, but was seen in 15% (15/101) of the cases of large cell non-keratinizing type cancer and 50% (8/16) of those of small cell non-keratinizing type cancer. No relationship was found between losses of A, B, and H antigens and parametrial spread of carcinoma or metastasis to the pelvic lymph nodes, but the incidence of death within 2 years after hysterectomy was higher in H antigen-negative cases than in H antigen-positive cases. These results indicate that loss of A and B antigens depends on some activity of invasion of cancer, while loss of H antigen strongly indicates dedifferentiation of cancer cells and also may indicate a poor prognosis. MH - ABO Blood-Group System/*IMMUNOLOGY ; Carcinoma in Situ/IMMUNOLOGY/ PATHOLOGY ; Carcinoma/*IMMUNOLOGY/PATHOLOGY ; Cervix Neoplasms/ *IMMUNOLOGY/PATHOLOGY ; Female ; Human ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis SO - Gynecol Oncol 1986 Oct;25(2):195-203 38 UI - 87002251 AU - Cox JD ; Samson MK ; Herskovic AM ; Abrams R ; Koehler M TI - Cisplatin and etoposide before definitive radiation therapy for inoperable squamous carcinoma, adenocarcinoma, and large cell carcinoma of the lung: a phase I-II study of the Radiation Therapy Oncology Group. AB - A trial of "neoadjuvant: cisplatin-etoposide and radiation therapy was conducted by the Radiation Therapy Oncology Group for non-small cell carcinoma of the lung limited to the thorax. Thirty evaluable patients were studied: two achieved complete response and four achieved partial response after chemotherapy. All patients underwent radiation therapy as planned, with no unusual acute reactions. Sixteen patients had local failure, and 13 had distant metastasis. Twenty-seven patients are dead, two are alive with cancer, and one is clinically free of cancer at 145 weeks. Five of six patients who survived greater than or equal to 2 years after treatment had adenocarcinomas. There was no unexpected late toxicity. This combination of chemotherapy and radiotherapy is unlikely to improve results in the treatment of inoperable non-small cell carcinoma of the lung over those with radiotherapy alone. MH - Actuarial Analysis ; Adenocarcinoma/*DRUG THERAPY/RADIOTHERAPY ; Adult ; Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Oat Cell/*DRUG THERAPY/RADIOTHERAPY ; Carcinoma, Squamous Cell/*DRUG THERAPY/RADIOTHERAPY ; Combined Modality Therapy ; Drug Evaluation ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY/RADIOTHERAPY ; Male ; Middle Age ; Radiotherapy, High Energy ; Support, U.S. Gov't, P.H.S. SO - Cancer Treat Rep 1986 Oct;70(10):1219-20 39 UI - 87002228 AU - Matthay RA ; Mahler DA ; Beck GJ ; Loke J ; Baue AE ; Carter DC ; Mitchell MS TI - Intratumoral Bacillus Calmette-Gu:erin immunotherapy prior to surgery for carcinoma of the lung: results of a prospective randomized trial. AB - A prospective randomized trial of preoperative intratumoral therapy with Bacillus Calmette-Gu:erin (BCG) was conducted in non-small cell lung cancer patients. Eighty-eight patients (48 BCG-treated and 40 control subjects) were entered into the study; three control subjects were removed from data analysis because histology revealed pathology other than non-small cell lung cancer. There were no differences between BCG-treated and control patients in sex, age, cigarettes smoked per day, pack-years of cigarette smoking, white blood cell count, or number of peripheral blood lymphocytes. Toxicity of BCG was limited to transient malaise and fever (average peak temperature, 38.7 degrees C). There was no significant difference in outcome (recurrence or survival) between BCG-treated and control groups with Stage I or Stage III tumors; there were too few Stage II tumors for separate statistical analysis. Outcome was not affected within or between the two treatment groups by tuberculin skin test status. Combining both treatment groups, Stage III patients had a worse outcome than did Stage I-II patients, non-squamous cell tumor patients (large cell and adenocarcinoma) had worse outcomes than did squamous cell tumor patients, and men had a worse outcome than women. We conclude that, although preoperative intratumoral BCG therapy is safe, it does not lengthen disease-free interval or prolong survival in patients with non-small cell lung cancer. MH - Bacterial Vaccines/ADMINISTRATION & DOSAGE ; Carcinoma/SURGERY/ *THERAPY ; Combined Modality Therapy ; Female ; Human ; Immunotherapy ; Lung Neoplasms/SURGERY/*THERAPY ; Male ; Middle Age ; Mycobacterium Bovis/*IMMUNOLOGY ; Prognosis ; Prospective Studies SO - Cancer Res 1986 Nov;46(11):5963-8 40 UI - 87002049 AU - Carmichael J ; Fergusson RJ ; Wolf CR ; Balkwill FR ; Smyth JF TI - Augmentation of cytotoxicity of chemotherapy by human alpha-interferons in human non-small cell lung cancer xenografts. AB - Three human non-small lung cancer xenograft lines were used to study the activity of combinations of cytotoxic drugs with human alpha-interferons (IFNs). Statistically significant potentiation of cis-platinum (CDDP) and cyclophosphamide (CY) given weekly in a low dose was seen when human lymphoblastoid interferon (IFN-alpha nl) (2 X 10(5) mu/mouse/day) was administered simultaneously. The median tumor doubling times for CDDP in the three tumors (35, 22, and 29 days) increased to 52, 51, and 41 days when IFN-alpha nl was added. A similar though less marked effect was seen with CY (median doubling time increased from 21.5, 19.5, and 27 days to 32, 27, and 35 days with the addition of IFN-alpha nl). IFN-alpha nl alone at this dosage was shown to have some cytotoxic activity. Similar potentiation of CDDP and ifosfamide was seen in two tumors when human recombinant alpha-2 interferon was added at a lower dose (2 X 10(4) mu/mouse/day). Median doubling times for CDDP increased from 17 and 14 days to 27 and 18.5 days with the addition of human recombinant alpha-2 interferon, whereas for ifosfamide they increased from 11.5 and 14 days to 15 and 16 days. Human recombinant alpha-2 interferon in this dose had no effect as a single agent. MH - Animal ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Non-Small Cell Lung/*THERAPY ; Cisplatin/ ADMINISTRATION & DOSAGE ; Human ; Ifosfamide/ADMINISTRATION & DOSAGE ; Interferon Type I/*ADMINISTRATION & DOSAGE ; Lung Neoplasms/*THERAPY ; Mice ; Mice, Inbred CBA ; Neoplasm Transplantation ; Transplantation, Heterologous SO - Cancer Res 1986 Oct;46(10):4916-20 41 UI - 86320045 AU - Abrams JS ; Cunat JS ; Whitley NO ; Fuks JZ ; Aisner J TI - CT evaluation of patients during treatment of advanced non-small cell lung carcinoma. AB - Twenty-one patients with Stage III non-small cell bronchogenic carcinoma were studied by chest radiograph and computed tomography (CT) before and after chemotherapy. In three patients (14%), the prechemotherapy CT showed measurable disease not seen on chest radiograph. Postchemotherapy CT scans showed additional measurable disease not seen on chest x-ray films in nine of 56 (16%) follow-up exams. This represented additional disease in seven of the 21 patients (33%). The CT findings resulted in a significant change in therapy in six of the 21 patients (29%). MH - Adult ; Aged ; Carcinoma, Bronchogenic/DRUG THERAPY/*RADIOGRAPHY ; Female ; Human ; Lung Neoplasms/DRUG THERAPY/*RADIOGRAPHY ; Male ; Middle Age ; Thoracic Radiography ; *Tomography, X-Ray Computed SO - Am J Clin Oncol 1986 Aug;9(4):292-8 42 UI - 86313710 AU - Hellstr:om I ; Beaumier PL ; Hellstr:om KE TI - Antitumor effects of L6, an IgG2a antibody that reacts with most human carcinomas. AB - Mouse monoclonal antibody L6 (IgG2a subtype) recognizes a ganglioside antigen expressed at the surface of cells from human non-small-cell lung carcinomas, breast carcinomas, and colon carcinomas. We now show that this antibody can lyse L6 antigen-positive human tumor cells in the presence of Leu-11b-positive human lymphocytes (i.e., mediate antibody-dependent cellular cytotoxicity) or human serum (mediate complement-dependent cytotoxicity) and that it can inhibit the outgrowth of an L6 antigen-positive human tumor transplanted onto nude mice. MH - Animal ; Antibodies, Monoclonal/*IMMUNOLOGY ; Antibodies, Neoplasm/*IMMUNOLOGY ; Antibody-Dependent Cell Cytotoxicity ; Antigens, Neoplasm/ANALYSIS ; Complement/IMMUNOLOGY ; Female ; Human ; IgG/*IMMUNOLOGY ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms/*IMMUNOLOGY ; Support, Non-U.S. Gov't SO - Proc Natl Acad Sci USA 1986 Sep;83(18):7059-63 43 UI - 86298192 AU - Miller TP ; Vance RB ; Ahmann FR ; Rodney SR TI - Extensive non-small cell lung cancer treated with mitomycin, cisplatin, and vindesine (MiPE): a Southwest Oncology Group Study. AB - Ninety-seven previously untreated patients with metastatic non-small cell lung cancer were treated with combination chemotherapy consisting of mitomycin (10 mg/m2) on Day 1, cisplatin (50 mg/m2) on Days 1 and 22, and vindesine (3 mg/m2) on Days 1 and 22 (MiPE). MiPE was repeated at 6-week intervals until disease progression or unacceptable toxicity. The overall response rate was 33%. There were seven complete responses (7%) and 25 partial responses (26%). The median progression-free interval for responding patients was 7 months. Median survival for all patients was 5 months, with 16% surviving 1 year. One patient died from sepsis while neutropenic. The results with MiPE treatment for patients with non-small cell lung cancer compare favorably to other mitomycin-vinca combinations previously tested in the Southwest Oncology Group. MH - Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Carcinoma/*DRUG THERAPY ; Cisplatin/ ADMINISTRATION & DOSAGE ; Clinical Trials ; Comparative Study ; Follow-Up Studies ; Human ; Lung Neoplasms/*DRUG THERAPY ; Mitomycins/ADMINISTRATION & DOSAGE ; Neoplasm Metastasis ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Vindesine/ ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Sep;70(9):1101-4 44 UI - 86298190 AU - Kris MG ; Gralla RJ ; Wertheim MS ; Kelsen DP ; O'Connell JP ; Burke MT ; Fiore JJ ; Cibas IR ; Heelan RT TI - Trial of the combination of mitomycin, vindesine, and cisplatin in patients with advanced non-small cell lung cancer. AB - In prior trials, mitomycin, vindesine, and cisplatin have each been shown to have reproducible antitumor activity as single agents when used in the treatment of patients with non-small cell lung cancer. The two-drug combinations of vindesine plus high-dose cisplatin or mitomycin have shown an improved major response rate and manageable toxicity in prior trials. In this report, 90 patients with stage III non-small cell lung cancer were treated with the three-drug combination of mitomycin (8 mg/m2), vindesine (3 mg/m2), and high-dose cisplatin (120 mg/m2). Eighty-seven patients (97%) were adequate for both response and toxicity. Major objective responses occurred in 60% of the patients. The toxicity of this regimen was predictable and manageable when established supportive care measures were employed. Based on the response rate observed, the combination of these three agents merits further study in randomized trials against other chemotherapeutic regimens and consideration of its use in adjuvant and preoperative settings. MH - Antineoplastic Agents, Combined/TOXICITY/*THERAPEUTIC USE ; Carcinoma/*DRUG THERAPY/PATHOLOGY ; Cisplatin/ADMINISTRATION & DOSAGE ; Clinical Trials ; Comparative Study ; Female ; Follow-Up Studies ; Human ; Lung Neoplasms/*DRUG THERAPY/PATHOLOGY ; Male ; Middle Age ; Mitomycins/ADMINISTRATION & DOSAGE ; Neoplasm Metastasis ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Vindesine/ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Sep;70(9):1091-6 45 UI - 86285814 AU - Garrett JE ; Breed MC TI - Changes in outcome for patients with bronchial carcinoma: the Green Lane Hospital experience. AB - To evaluate the effect of changes in the management of bronchial carcinoma at Green Lane Hospital, we have made a retrospective analysis of patients presenting in 1978 and 1979. Previous reviews from this unit provided a comparison. There was a modest improvement in the 5-year survival for the group as a whole (4.3% in 1955-65 to 7.7% in 1978-79). For patients undergoing surgical resection, the improvement in 5-year survival from 22% to 40.5% appeared mainly due to better pre-operative selection. Patients with non-small-cell carcinoma selected for radical radiotherapy had a 5-year survival of 7.2%. During the study period, radiotherapy alone was replaced by a combination of chemotherapy and radiotherapy for limited small-cell carcinoma. Median survival improved from six months to 13.5 months and was better than the 7.5 months obtained with surgical resection in 1955-65. Twenty-four patients were referred as a result of mass miniature x-ray (MMR) at a rate of 22/100 000 radiographs taken. Five-year survival for the MMR group was statistically better than for the rest of the group (29% compared to 7.2%; p less than 0.001), supporting the practice of x-raying smokers over the age of 45 annually. MH - Adult ; Aged ; Carcinoma/*MORTALITY/THERAPY ; Female ; Human ; Lung Neoplasms/*MORTALITY/THERAPY ; Male ; Middle Age ; New Zealand ; Support, Non-U.S. Gov't SO - NZ Med J 1986 Jun 25;99(804):455-8 46 UI - 86282297 AU - Tamura T ; Saijo N ; Shinkai T ; Eguchi K ; Sasaki Y ; Sakurai M ; Sano T ; Keicho N ; Morinaga S TI - A case report of a three-year survivor with advanced non-small cell lung cancer producing alpha-fetoprotein. AB - An 80-year-old patient with poorly differentiated adenocarcinoma of the left lung with metastasis to both lungs and supraclavicular lymph nodes, stage III M1 (T2N2M1), was treated with cisplatin (cis-diamminedichloroplatinum, CDDP) at a dose of 80 mg/m2 intravenously. He achieved a partial response, however, he could not continue therapy with CDDP because of its renal toxicity. He was then given etoposide and vindesine as a single chemotherapeutic agent, but no response was observed. Therefore, CDDP was administered again in a fractionated regimen, the first course of treatment achieved a minor response, but the second course resulted in stable disease. He therefore received combination chemotherapy consisting of mitomycin, vindesine and CDDP, and tumor regression of more than 30% was observed after one course of this combination chemotherapy. After three years from the initiation of chemotherapy, he had no symptoms except for hoarseness, and has been followed up on an ambulatory basis. In addition, the tumor was producing alpha-fetoprotein (AFP), which was shown by immunohistochemical staining with polyclonal antibody against AFP. The changes in serum AFP level correlated well with the disease status. MH - Adenocarcinoma/*DRUG THERAPY ; Aged ; Alpha Fetoproteins/ *BIOSYNTHESIS ; Antineoplastic Agents, Combined/THERAPEUTIC USE ; Case Report ; Cisplatin/*THERAPEUTIC USE ; Human ; Lung Neoplasms/ *DRUG THERAPY/METABOLISM ; Male ; Prognosis ; Support, Non-U.S. Gov't ; Time Factors SO - Jpn J Clin Oncol 1986 Jun;16(2):175-81 47 UI - 86280830 AU - Moss F ; Bobrow LG ; Sheppard MN ; Griffiths M ; Rowe D ; Beverley PC ; Addis B ; Souhami RL TI - Expression of epithelial and neural antigens in small cell and non small cell lung carcinoma. AB - Seventy-one lung carcinomas from 66 different patients were stained with a panel of monoclonal antibodies. Twenty-nine were small cell lung carcinoma (SCLC), 15 adenocarcinomas, 17 squamous carcinomas and 10 large cell carcinomas. Three of the monoclonal antibodies recognize different cytokeratins, three recognize other epithelial antigens and one recognizes a neural antigen. Both formalin-fixed and cryopreserved tumours were studied using an indirect immunoperoxidase method. 23/29 SCLC reacted with all but one of the antibodies which recognize epithelial antigens. This staining was similar to that seen in non small cell lung carcinomas (NSCLC) and provides further evidence that SCLC are true epithelial tumours. All but one of the SCLC stained with the antibody recognizing a neural antigen. This antibody did not stain squamous or adenocarcinomas. However, four of the large cell carcinomas stained well with this antibody, suggesting that SCLC and some large cell carcinomas share a common pathway of differentiation. There were variations of staining seen both within and between tumours. This has obvious implications if immunotargetting with monoclonal antibodies is to be used diagnostically or therapeutically. MH - Adenocarcinoma/IMMUNOLOGY ; Antibodies, Monoclonal/IMMUNOLOGY ; Antigens, Neoplasm/*ANALYSIS ; Carcinoma/IMMUNOLOGY ; Carcinoma, Oat Cell/*IMMUNOLOGY ; Carcinoma, Squamous Cell/IMMUNOLOGY ; Epithelium/IMMUNOLOGY ; Human ; Lung Neoplasms/*IMMUNOLOGY ; Neurons/IMMUNOLOGY ; Stains and Staining SO - J Pathol 1986 Jun;149(2):103-11 48 UI - 86271837 AU - Goodman GE TI - Phase II trial of retinol in patients with advanced cancer. AB - We have completed a phase II trial of oral retinol (200,000 units/m2) in 65 patients with advanced cancer. All patients were followed at 4-week intervals for tumor response and clinical or chemical evidence of toxicity. Seventeen patients had non-small cell lung cancer, 15 had melanoma, 12 had adenocarcinoma of the colon, and 17 had miscellaneous tumors. There were one partial response, five mixed responses, two patients with stable disease, and 47 patients with progressive disease. Thirty-seven of 60 patients reported no side effects; 13 developed mild cutaneous symptoms; and 12 developed reversible central nervous system symptomatology. Oral retinol appears to have limited activity in patients with advanced cancer. MH - Adenocarcinoma/*DRUG THERAPY ; Adult ; Aged ; Colonic Neoplasms/ *DRUG THERAPY ; Drug Evaluation ; Female ; Human ; Lung Neoplasms/ *DRUG THERAPY ; Male ; Melanoma/*DRUG THERAPY ; Middle Age ; Skin Diseases/CHEMICALLY INDUCED ; Support, Non-U.S. Gov't ; Vitamin A/ ADVERSE EFFECTS/*THERAPEUTIC USE SO - Cancer Treat Rep 1986 Aug;70(8):1023-4 49 UI - 86271802 AU - Meyer TJ ; Pearlman NW ; Siebert PE ; Murphy JR ; White MJ ; Zaloznik A ; Braun T ; Rempel P TI - Comparison of alternating to nonalternating chemotherapy regimens for non-small cell lung cancer. AB - Forty-seven patients with stage III lung cancer from four institutions in the Denver area were entered in a study comparing two regimens of chemotherapy. The patients were randomized into two groups: Group A received lomustine, cyclophosphamide, vincristine, cisplatin, and doxorubicin monthly; Group B received the five-drug regimen on Months 1, 3, and 5 and received 5-FU by constant infusion, methotrexate, and mitomycin on Months 2, 4, and 6. The age, extent of disease, Karnofsky score, prior therapy, and average number of chemotherapy courses received in each group were comparable. The median survival in Group A was 265 days and in Group B was 163 days (P greater than 0.25). There does not seem to be an advantage in survival in patients who are treated with the eight-drug regimen over the five-drug regimen. MH - Adenocarcinoma/*DRUG THERAPY/MORTALITY ; Adult ; Aged ; Antineoplastic Agents, Combined/MORTALITY/*THERAPEUTIC USE ; Carcinoma, Oat Cell/*DRUG THERAPY/MORTALITY ; Carcinoma, Squamous Cell/*DRUG THERAPY/MORTALITY ; Comparative Study ; Drug Administration Schedule ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Neoplasm Metastasis ; Random Allocation ; Time Factors SO - Cancer Treat Rep 1986 Jun;70(6):711-4 50 UI - 86271768 AU - Sobol RE ; Peters RE ; Astarita RW ; Hofeditz C ; Masui H ; Burton D ; Handley HH ; Glassy MC ; Fairshter R ; Carlo DJ ; et al TI - A novel monoclonal antibody-defined antigen which distinguishes human non-small cell from small cell lung carcinomas. AB - Spleen cells from BALB/c mice hyperimmunized with the human epidermoid lung carcinoma cell line T222 were fused with NS-1 mouse myeloma cells to produce monoclonal antibodies to human lung cancer antigens. Hybridoma culture supernatants were tested by an enzyme-linked immunosorbent assay for reactivity against a panel of human lung tumor cell lines. Supernatant from hybridoma EA1 (immunoglobulin G1) displayed strong reactivity with four of four non-small cell lung carcinomas but did not react with three of three small cell lung carcinoma (SCLC) cell lines. This hybridoma was cloned by limiting dilution and utilized to generate ascites antibody for subsequent immunohistochemical and antigen characterization studies. Evaluation of fresh frozen tumor tissue sections by immunoperoxidase staining methods revealed EA1 reactivity with the vast majority of non-SCLCs tested (21 of 21 epidermoid, 17 of 18 adenocarcinomas, four of four large cell, two of two bronchioloalveolar) and no reactivity with nine of nine small cell lung carcinomas. EA1 also stained bronchial epithelium and other benign and malignant epithelial tissues. The EA1 antigen was determined to have a molecular weight of 75,000 by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human non-SCLC tumor extracts. These data imply that EA1 recognizes a novel antigen expressed by non-SCLCs and other epithelial tissues. The absence of EA1 reactivity with SCLCs suggests that this monoclonal antibody may find future application in distinguishing non-SCLC from SCLC and prove useful in furthering our understanding of the histogenesis of lung carcinomas. MH - Adenocarcinoma/*IMMUNOLOGY ; Antibodies, Monoclonal/*IMMUNOLOGY ; Antigens, Neoplasm/*IMMUNOLOGY ; Antigens, Surface/IMMUNOLOGY ; Carcinoma, Oat Cell/*IMMUNOLOGY ; Carcinoma, Squamous Cell/ *IMMUNOLOGY ; Cell Line ; Cell Membrane/IMMUNOLOGY ; Epithelium/ IMMUNOLOGY ; Human ; Lung/IMMUNOLOGY ; Lung Neoplasms/*IMMUNOLOGY ; Molecular Weight ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Sep;46(9):4746-50 51 UI - 86271624 AU - Hellstr:om I ; Horn D ; Linsley P ; Brown JP ; Brankovan V ; Hellstr:om KE TI - Monoclonal mouse antibodies raised against human lung carcinoma. AB - We have evaluated approximately 10,000 monoclonal antibodies (MoAb) resulting from 25 hybridizations of spleen cells from mice immunized with cells from human non-small cell lung carcinoma or fetal lung. The spleen cells were hybridized with NS-1 myeloma cells, and the resulting hybridomas were screened for production of MoAb to non-small cell lung carcinoma by binding assays with either cell extracts or cells growing in culture, followed by immunohistology on frozen sections. Fourteen MoAb had relative specificity for non-small cell lung carcinoma versus normal tissues. Three of these MoAb (L3, L6, L17) also reacted with most carcinomas of the breast and colon, and two MoAb (L20 and L22) reacted with the four samples of small cell lung carcinoma tested. No MoAb defined an antigen of absolute tumor specificity, and no MoAb reacted substantially more with adenocarcinoma than squamous cell carcinoma of the lung (or vice versa). Five MoAb were Ig G1, two were Ig G2a, and the remaining seven were Ig M. Seven MoAb (L5, L6, L15, L17, L20, L22, L23) could bind to the cell surface. Three MoAb (L6, L15, L17) defined carbohydrate antigens, and three (L3, L5, L20) were to protein antigens, while the antigens to which the remaining MoAb are directed have not been identified. Six MoAb could bind to tumor cells in Carnoy-fixed paraffin-embedded sections. An intercellular variability in antigen expression was detected with all 14 MoAb. At least two of the MoAb, L6 and L20, are good candidates for preclinical testing in view of their high level of tumor selectivity, as shown by both immunohistology and binding assays with living cells. MH - Animal ; Antibodies, Monoclonal/DIAGNOSTIC USE/*IMMUNOLOGY ; Antigens, Neoplasm/*ANALYSIS ; Carcinoma/*IMMUNOLOGY ; Human ; Hybridomas ; Lung/IMMUNOLOGY ; Lung Neoplasms/*IMMUNOLOGY ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Support, Non-U.S. Gov't SO - Cancer Res 1986 Aug;46(8):3917-23 52 UI - 86271547 AU - Davis S ; Tonato M ; Crin:o L ; Colozza MA ; Lubansky K ; Grignani F TI - Cisplatin, etoposide, and mitomycin in the treatment of non-small cell carcinoma of the lung. A pilot study. AB - A total of 39 patients with non-small cell carcinoma of the lung (NSCL) were treated with cisplatin, etoposide, and mitomycin. A major response rate (complete response + partial response) was seen in 15 patients (39%). Median survival for all patients was 340 days; median survival of the responding group was 514 days. Toxic effects included moderate hematologic toxicity, nausea, and vomiting. There were no treatment-related deaths. This regimen clearly is effective in treating NSCL. MH - Adenocarcinoma/*DRUG THERAPY/PATHOLOGY ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/*THERAPEUTIC USE ; Carcinoma, Oat Cell/*DRUG THERAPY/PATHOLOGY ; Carcinoma, Squamous Cell/*DRUG THERAPY/PATHOLOGY ; Cisplatin/ADMINISTRATION & DOSAGE ; Drug Evaluation ; Etoposide/ADMINISTRATION & DOSAGE ; Human ; Lung Neoplasms/*DRUG THERAPY/PATHOLOGY ; Middle Age ; Mitomycins/ ADMINISTRATION & DOSAGE ; Pilot Projects SO - Cancer 1986 Sep 1;58(5):1018-9 53 UI - 86271517 AU - Mandell L ; Hilaris B ; Sullivan M ; Sundaresan N ; Nori D ; Kim JH ; Martini N ; Fuks Z TI - The treatment of single brain metastasis from non-oat cell lung carcinoma. Surgery and radiation versus radiation therapy alone. AB - Between 1978-1980, 104 patients with single brain metastases (SBM) from non-small cell lung carcinoma (NSCLC) were treated at Memorial Sloan-Kettering Cancer Center (MSKCC). These included 35 patients treated with surgical resection and radiation (S + ERT) and 69 patients treated with conventional external beam radiation therapy alone (ERT). Surgical resection was combined with whole brain (WBRT) and focal radiation in 83% and 17% of patients, respectively. In the ERT group, all patients received WBRT. Both treatment groups were similar with regard to age, sex, stage distribution, location and size of SBM, and time to relapse from initial diagnosis of NSCLC. The histologic examination, however, revealed adenocarcinoma predominating in those patients receiving S + ERT and epidermoid carcinoma in those receiving ERT. Follow-up treatment, symptomatic, and CTT response rates were evaluated. With S + ERT, the overall subjective and objective responses were 80% and 87%, respectively, and with ERT, 83% and 72% (of the 47 patients available for follow-up CT scans), respectively. Survival data indicate a significant advantage of S + ERT over ERT with a median survival of 16 months versus 4 months (P less than 0.0001). Three major factors, however, may have contributed to this difference: (1) patients in the S + ERT group generally received more aggressive initial treatment to the primary disease in the lung (72%) compared to the ERT group (36%); (2) in the S + ERT group, extracranial disease was absent at the time of SBM diagnosis in 49% of the S + ERT group compared to 26% in the ERT group; and (3) distant metastases were present in only 6% of the surgical patients yet, they were present in 49% of those treated with radiation alone. In one subset of patients, however--those with a radically treated primary and no extracranial disease--S + ERT resulted in a median survival of 33 months with 33% of the population still alive with no evidence of disease compared to 12 months and 0%, respectively, with ERT alone. Moreover, intracranial relapse was the cause of death in only one S + ERT patient (9%), yet it accounted for 50% of the ERT deaths. These data suggest that an aggressive approach to SBM in such favorable prognostic patients may indeed improve survival. MH - Adenocarcinoma/MORTALITY/RADIOTHERAPY/SECONDARY/SURGERY ; Adult ; Aged ; Brachytherapy ; Brain/SURGERY ; Brain Neoplasms/MORTALITY/ RADIOTHERAPY/*SECONDARY/SURGERY ; Carcinoma, Squamous Cell/ MORTALITY/RADIOTHERAPY/SECONDARY/SURGERY ; Combined Modality Therapy ; Comparative Study ; Female ; Human ; Lung Neoplasms/ MORTALITY/RADIOTHERAPY/*SURGERY ; Male ; Middle Age ; Neoplasm Staging ; Retrospective Studies SO - Cancer 1986 Aug 1;58(3):641-9 54 UI - 86265449 AU - Albain KS ; Hoffman PC ; Little AG ; Bitran JD ; Golomb HM ; DeMeester TR ; Griem ML ; Blough RR ; Skosey C TI - Pleural involvement in stage IIIM0 non-small-cell bronchogenic carcinoma. A need to differentiate subtypes. AB - Forty-one patients with two subtypes of stage IIIM0 non-small-cell lung cancer treated over a 7-year period were evaluated. The first group of 20 patients had ipsilateral parietal pleural involvement not contiguous with the primary tumor but no distant metastases. Fifteen had positive pleural fluid cytology, seven with positive pleural biopsy in addition; four had extensive pleural studding or a positive biopsy but no effusion; and one had negative pleural fluid cytology. Treatment consisted of radiation therapy followed by combination chemotherapy in all. Due to symptoms, eight patients first had fluid drainage with or without sclerosis and two patients had a pleurectomy. Nine had progressive pleural disease despite the local treatment. To all modalities of therapy, only two patients had a partial response. One patient who had a pleurectomy lived 25 months. Median survival was 6.9 months. Cause of failure involved local progression in 17 patients. There was no difference in median survival by age, sex, histology, side of effusion, location of nodal disease, or use of local therapy. The second group of 21 patients had localized involvement of the parietal pleura by the primary tumor. There was deeper chest wall invasion in nine. All patients were rendered free of known disease by surgical resection, were stage T3N0-2M0, and received radiation and chemotherapy in addition to resection. The median survival was 13.5 months. There was local recurrence in nine patients but only one developed an effusion. Five patients were alive at 29-82 months. No variable unfavorably influenced survival except a central versus peripheral primary. Thus, the median survival of the patients in the first group with multiple sites of pleural involvement was similar to that of patients with distant metastases but with the cause of failure primarily local progression. In the majority of patients in the second group, parietal pleural and chest wall involvement, even with nodal metastases, did not translate into local failure, and long-term survival was possible. MH - Age Factors ; Carcinoma, Bronchogenic/*PATHOLOGY ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/*PATHOLOGY ; Male ; Middle Age ; Pleural Effusion/COMPLICATIONS ; Pleural Neoplasms/MORTALITY/*SECONDARY/THERAPY ; Sex Factors SO - Am J Clin Oncol 1986 Jun;9(3):255-61 55 UI - 86265446 AU - Laramore GE ; Bauer M ; Griffin TW ; Thomas FJ ; Hendrickson FR ; Maor MH ; Griffin BR ; Saxton JP ; Davis LW TI - Fast neutron and mixed beam radiotherapy for inoperable non-small cell carcinoma of the lung. Results of an RTOG randomized study. AB - From July 1979 through March 1984 the Radiation Therapy Oncology Group conducted a randomized study comparing fast neutron radiotherapy versus mixed beam (neutron/photon) radiotherapy versus conventional radiotherapy for patients with non-small cell carcinoma of the lung. Patients were either medically or technically inoperable. One hundred two evaluable patients were placed on the study. The radiation doses were approximately 60 Gy-equivalent on each arm. Patients were stratified according to size of primary, histology, Karnofsky performance status, and age distribution. Overall local response rates as measured by serial radiographs were the same on the three arms, and an actuarial analysis showed no significant differences in either median or long-term survival. However, for the subgroup of patients exhibiting a complete or partial tumor response at 6 months there was a suggestion of improved 3-year survival on the two experimental arms (mixed beam, 37%; neutrons, 25%; photons, 12%). The p value for the difference between the mixed beam and photon curves is 0.14 (two-sided test). The incidence of major complications was higher on the neutron and mixed beam arms. These complications included four cases of myelitis which are analyzed in detail. The results are placed in the context of other published work on the use of neutrons in the treatment of lung cancer. MH - Comparative Study ; Fast Neutrons/*THERAPEUTIC USE ; Human ; Lung Neoplasms/*RADIOTHERAPY ; Myelitis/ETIOLOGY ; Neutrons/ *THERAPEUTIC USE ; Radiation Injuries ; Radiotherapy/ADVERSE EFFECTS ; Random Allocation ; Risk ; Support, U.S. Gov't, P.H.S. SO - Am J Clin Oncol 1986 Jun;9(3):233-43 56 UI - 86253514 AU - Mooi WJ ; Van Zandwijk N ; Dingemans KP ; Koolen MG ; Wagenvoort CA TI - The 'grey area' between small cell and non-small cell lung carcinomas. Light and electron microscopy versus clinical data in 14 cases. AB - We studied 14 lung tumours which on light microscopy had posed difficulties on classification as either small cell or non-small cell carcinomas. The light and electron microscopical features were compared with patient follow-up data. Electron microscopy showed neuroendocrine granules in 12 cases, and adeno- and squamous cell differentiation but no neuroendocrine granules in the remaining two cases. The latter two cases showed prolonged patient survival (both patients alive after 2 1/2 and 2 years, respectively). Ten of the cases with neuroendocrine granules showed a rapid course of disease (death between 2 1/2 weeks and 15 months after diagnosis) and marked initial response to multiagent chemotherapy. Thus, the clinical impression of these cases was that of small cell carcinoma. The remaining two cases with neuroendocrine granules showed a more protracted course, with death after 1 1/2 and 2 1/2 years. These two tumours did not show the light microscopical features of atypical carcinoid. The results illustrate the value of electron microscopy in predicting clinical behaviour of carcinomas difficult to place into small cell or non-small cell carcinoma groups. They also point to the existence of neuroendocrine carcinomas other than carcinoids with a more protracted course than small cell carcinomas. MH - Adult ; Aged ; Carcinoma, Oat Cell/*PATHOLOGY/ULTRASTRUCTURE ; Carcinoma, Squamous Cell/PATHOLOGY/ULTRASTRUCTURE ; Cytoplasmic Granules/PATHOLOGY/ULTRASTRUCTURE ; Human ; Lung Neoplasms/ CLASSIFICATION/*PATHOLOGY/ULTRASTRUCTURE ; Male ; Microscopy, Electron ; Middle Age SO - J Pathol 1986 May;149(1):49-54 57 UI - 86253513 AU - Mooi WJ ; Dingemans KP ; Van Zandwijk N TI - Prevalence of neuroendocrine granules in small cell lung carcinoma. Usefulness of electron microscopy in lung cancer classification. AB - Fifty-four lung carcinomas submitted for routine electron microscopy under the light microscopical diagnosis of small cell carcinoma were investigated. In 42 or of 45 evaluable cases, neuroendocrine granules were considered definitely or probably present, the modification 'probably' being necessary in suboptimal material. In three cases, squamous cell differentiation was seen, but no neuroendocrine granules were found. On revision of these three cases, the light microscopical diagnosis was changed to squamous cell carcinoma in one instance, and neither of the other two cases was considered classical for small cell carcinoma. Patient follow-up of these three cases showed tumour behaviour indicative of non-small cell carcinoma in two evaluable cases, the third case yielding no significant data. These results indicate that neuroendocrine granules can generally be found in small cell lung carcinomas, provided the material is sufficient for evaluation. When these granules are absent, and other differentiation is found on electron microscopy, the final classification of the tumour should incorporate this finding, to warn the clinician that the tumour will not necessarily behave as a small cell carcinoma. MH - Carcinoma, Oat Cell/*ULTRASTRUCTURE ; Carcinoma, Squamous Cell/ ULTRASTRUCTURE ; Cytoplasmic Granules/ULTRASTRUCTURE ; Human ; Intracellular Membranes/ULTRASTRUCTURE ; Lung Neoplasms/ CLASSIFICATION/*ULTRASTRUCTURE ; Microscopy, Electron SO - J Pathol 1986 May;149(1):41-7 58 UI - 86219438 AU - Eichenhorn MS ; Kvale PA ; Miks VM ; Seydel HG ; Horowitz B ; Radke JR TI - Initial combination therapy with YAG laser photoresection and irradiation for inoperable non-small cell carcinoma of the lung. A preliminary report. AB - Patients presenting with inoperable non-small cell carcinoma of the lung and major symptomatic bronchial obstruction were treated initially with debulking of the airways by YAG laser, followed by conventional external-beam radiotherapy. The former method was used to minimize postobstructive pneumonitis or respiratory failure (or both) that often complicates major brochial obstruction and also to lessen the burden of tumor to be treated by radiotherapy. The preliminary results of 19 patients treated in this manner are reported, emphasizing the impact of this combined method on morbidity and mortality. MH - Adenocarcinoma/RADIOTHERAPY/SURGERY ; Aged ; Carcinoma/ RADIOTHERAPY/*SURGERY ; Carcinoma, Bronchogenic/RADIOTHERAPY/ SURGERY ; Carcinoma, Squamous Cell/RADIOTHERAPY/SURGERY ; Combined Modality Therapy ; Female ; Human ; Lasers/*THERAPEUTIC USE ; Lung Neoplasms/RADIOTHERAPY/*SURGERY ; Male ; Middle Age ; Postoperative Complications SO - Chest 1986 Jun;89(6):782-5 59 UI - 86217770 AU - Falzon M ; McMahon JB ; Schuller HM ; Boyd MR TI - Metabolic activation and cytotoxicity of 4-ipomeanol in human non-small cell lung cancer lines. AB - In the normal lungs of many animal species, 4-ipomeanol is transformed to a highly reactive metabolite preferentially in pulmonary bronchiolar Clara cells and to a lesser extent in alveolar type II cells, potentially leading to damage or destruction of these cell types. Since Clara cells and type II cells are suspected sites of origin of certain "non-small cell: lung cancers, the metabolic activation of 4-ipomeanol (measured by the metabolism-dependent covalent binding of 4-ipomeanol to cellular macromolecules) was compared in two human non-small cell carcinoma derived cell lines (NCI-H322 and NCI-H358) and two human small cell carcinoma derived cell lines (NCI-H128 and NCI-H69). Metabolic activation of 4-ipomeanol was evident in the non-small cell lines; the production of covalently bound metabolite was somewhat greater in NCI-H322 (morphology related to Clara cells) compared to NCI-H358 (morphology related to alveolar type II cells), but was entirely undetectable in the small cell lines. The activation pathway was concentration (4-ipomeanol) and time dependent and followed Michaelis-Menten kinetics. Metabolism to the reactive intermediate required oxygen and was strongly inhibited by carbon monoxide. Covalent binding was enhanced in the non-small cell lines by prior incubation with beta-naphthoflavone and by supplementation of the incubate with exogenous reduced nicotinamide adenine dinucleotide phosphate. 4-Ipomeanol was more cytotoxic to the non-small cell lines than to the small cell lines under the in vitro growth conditions used. These studies indicate that certain human non-small cell lung cancers have metabolic characteristics of normal bronchiolar Clara cells and alveolar type II cells; these results would therefore be consistent with an origin of these tumors from Clara cells or type II cells, respectively. The present studies indicate that the further preclinical testing and development of 4-ipomeanol is warranted, with a view toward possible clinical evaluation against human lung cancers. MH - Biotransformation ; Bronchi/METABOLISM/PATHOLOGY ; Carcinoma, Oat Cell/METABOLISM ; Cell Line ; Cell Survival/DRUG EFFECTS ; Human ; Lung Neoplasms/*METABOLISM/PATHOLOGY ; Mixed Function Oxidases/ METABOLISM ; Protein Binding ; Proteins/METABOLISM ; Pulmonary Alveoli/METABOLISM/PATHOLOGY ; Terpenes/*METABOLISM SO - Cancer Res 1986 Jul;46(7):3484-9 60 UI - 86216710 AU - Dorreen MS TI - Role of biological markers and probes in lung carcinomas. AB - Bronchial carcinomas are frequently associated with ectopic secretion of hormones which may be responsible for paraneoplastic syndromes. In non small cells carcinomas, serum calcitonin levels may be raised. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (responsible for gynaecomastia) in large cells carcinomas. In small carcinomas, many hormones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embryonic antigen add nothing to the information available with standard staging investigations. More recent studies have identified three protein products: the BB-isoenzyme of creatine kinase, bombesin and neurone-specific enolase. The latter seems a promising marker to follow up the course of the disease. MH - Adenocarcinoma/IMMUNOLOGY ; Apud Cells/METABOLISM ; Bombesin/ BLOOD/METABOLISM ; Carcinoma, Oat Cell/BLOOD/METABOLISM ; Carcinoma, Squamous Cell/METABOLISM ; Creatine Kinase Isoenzymes/ BLOOD/METABOLISM ; Hormones/BLOOD/METABOLISM ; Human ; Lung Neoplasms/BLOOD/DIAGNOSIS/*METABOLISM ; Neoplasm Staging ; Oncogenes ; Phosphopyruvate Hydratase/METABOLISM ; Prognosis ; Review SO - Bull Eur Physiopathol Respir 1986 Mar-Apr;22(2):137-46 61 UI - 86215956 AU - Reeve JG ; Stewart J ; Watson JV ; Wulfrank D ; Twentyman PR ; Bleehen NM TI - Neuron specific enolase expression in carcinoma of the lung. AB - The value of neuron specific enolase (NSE) immunoreactivity as a marker for small cell lung cancer (SLC) has been assessed using a monoclonal antibody (MCAB) against NSE, MCAB specificity was confirmed using purified enolase isoenzymes, sections of human brain, a panel of lung tumours, neuroendocrine and non-neuroendocrine tumours and normal tissues. Using this MCAB in radioimmunoassay and immunohistochemistry, NSE immunoreactivity was detected in all SCLC material examined. However, considerable reactivity was also observed in a number of non-small cell lung cancer cell lines and tumour biopsy specimens. Furthermore, intratumoral heterogeneity with respect to NSE immunostaining was observed in several cases. Factors which may underlie such intratumoral phenotypic diversity were assessed using flow cytometry together with MCABs directed against both NSE and non-neuronal enolase. Such studies revealed that enolase expression in cells which were no longer actively proliferating differed markedly from that of cells in exponential growth. Furthermore, cells grown under conditions of increasing hypoxia exhibited increased enolase expression relative to those grown under oxygenated conditions. It is concluded from these studies that NSE immunoreactivity per se is an unreliable marker for the SCLC phenotype. MH - Animal ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Carcinoma, Oat Cell/*ENZYMOLOGY/IMMUNOLOGY ; Cell Cycle ; Cell Line ; Cells, Cultured ; Female ; Human ; Immunoenzyme Technics ; Lung Neoplasms/*ENZYMOLOGY/IMMUNOLOGY ; Mice ; Mice, Inbred BALB C ; Phosphopyruvate Hydratase/IMMUNOLOGY/*METABOLISM SO - Br J Cancer 1986 Apr;53(4):519-28 62 UI - 86215946 AU - Heighway J ; Thatcher N ; Cerny T ; Hasleton PS TI - Genetic predisposition to human lung cancer. AB - The influence of polymorphic variants of the human c-Ha-ras gene on predisposition to lung cancer has been investigated. The human c-Ha-ras gene has been shown to reside on a polymorphic BamH1 restriction fragment. This restriction fragment length polymorphism (RFLP) results from variation in the size of a region of repetitive DNA 3' to the gene. An attempt has been made to characterise and compare the c-Ha-ras RFLP's in a normal population and in a group of cancer patients. DNA was extracted from the white blood cells of 101 normal donors and four common Ha-ras alleles identified, with occasional rare alleles of various sizes. The allele frequencies were examined in 132 lung cancer patients, comprising 66 individuals with small cell carcinoma of the lung (SCCL) and 66 with non-small cell carcinoma of the lung (non-SCCL). An abnormal allele distribution was found in individuals with non-SCCL compared to both control and SCCL values suggesting a degree of genetic pre-position to non-SCCL. In addition, analysis of the Ha-ras RFLP's in solid samples inferred a deletion of material from the short arm of chromosome 11 in two of 16 informative samples. MH - Adenocarcinoma/FAMILIAL & GENETIC ; Alleles ; Carcinoma, Oat Cell/ FAMILIAL & GENETIC ; Carcinoma, Squamous Cell/FAMILIAL & GENETIC ; Comparative Study ; Gene Frequency ; Genes ; Human ; Lung Neoplasms/*FAMILIAL & GENETIC ; Polymorphism (Genetics) ; Support, Non-U.S. Gov't ; Variation (Genetics) SO - Br J Cancer 1986 Apr;53(4):453-7 63 UI - 86211328 AU - Enig B ; Winther E ; Hessov I TI - Energy and protein intake and nutritional status in non-surgically treated patients with small cell anaplastic carcinoma of the lung. AB - The spontaneous food intake and nutritional status was assessed in 23 patients with small cell anaplastic carcinoma of the lung before and two times during a treatment period of 6 weeks. Radiation therapy was given for 2 weeks followed by a course of chemotherapy and another 2 weeks of radiation therapy. The energy intake decreased during the treatment from 146 to 130 per cent of basal metabolic rate (p greater than 0.10). The protein intake remained unchanged (mean 0.9 g/kg body weight). There were insignificant and small losses of weight, body fat, free body mass and arm muscle circumference, and no changes were seen in serum albumin and serum transferrin. However, 6 patients suffered a weight loss of 5 per cent or more. No correlation existed between the nutritional parameters measured before treatment and the changes during treatment. Patients who suffered a loss of body weight could therefore not be singled out before the treatment. MH - Carcinoma, Oat Cell/DRUG THERAPY/*METABOLISM/RADIOTHERAPY/THERAPY ; Combined Modality Therapy ; Dietary Proteins/METABOLISM ; Energy Metabolism ; Human ; Lung Neoplasms/DIET THERAPY/DRUG THERAPY/*METABOLISM/RADIOTHERAPY ; Nutrition ; Serum Albumin/ METABOLISM ; Support, Non-U.S. Gov't ; Transferrin/BLOOD SO - Acta Radiol [Oncol] 1986 Jan-Feb;25(1):19-22 64 UI - 86198833 AU - Finkelstein DM ; Ettinger DS ; Ruckdeschel JC TI - Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study. AB - Between December 1979 and June 1983 the Eastern Cooperative Oncology Group (ECOG) treated 893 good-performance status patients with metastatic non-small-cell lung cancer (NSCLC) on one of seven phase III combination chemotherapies. The overall median survival was 23.5 weeks with no significant differences between treatments. One hundred sixty-eight patients (19%) survived greater than 1 year and 36 (4%) for greater than 2 years. The etoposide-platinum combination had the highest proportion of 1-year survivors (25%). Mitomycin-vinblastine-platinum (MVP), which had demonstrated the highest response rate, had significantly fewer 1-year survivors (12%) than any other regimen (P = .003). Analysis of pretreatment characteristics that distinguished patients who survived greater than 1 year from those who did not demonstrated that an initial performance status of 0, no bone metastases, female sex, no subcutaneous metastases, non-large-cell histology, less than 5% prior weight loss, no symptoms of shoulder or arm pain, and no liver metastases were predictors of longer survival. Of particular interest was the finding that response duration was significantly longer (P = .002) for those patients who experienced a longer time to best response. In addition, patients who survived greater than 1 year experienced greater degrees of nonlethal toxicity, in particular, gastrointestinal and hematologic, than patients who did not survive 1 year, (P = .006). A detailed chart review of 32 2-year survivors and 32 matched controls demonstrated that maintenance or improvement of performance status and maintenance of serum albumin levels at 3 months from the initiation of treatment were both important predictors of longer survival. MH - Adenocarcinoma/BLOOD/DRUG THERAPY/MORTALITY ; Aged ; Alkaline Phosphatase/BLOOD ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/THERAPEUTIC USE ; Body Weight/DRUG EFFECTS ; Carcinoma, Bronchogenic/BLOOD/DRUG THERAPY/*MORTALITY ; Carcinoma, Squamous Cell/BLOOD/DRUG THERAPY/MORTALITY ; Comparative Study ; Cyclophosphamide/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Doxorubicin/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Etoposide/ ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Female ; Human ; Lung Neoplasms/BLOOD/DRUG THERAPY/*MORTALITY ; Male ; Methotrexate/ ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Middle Age ; Mitomycins/ ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Neoplasm Metastasis ; Procarbazine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Progesterone/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Prognosis ; Serum Albumin/ANALYSIS ; Support, U.S. Gov't, P.H.S. ; Vinblastine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS SO - J Clin Oncol 1986 May;4(5):702-9 65 UI - 86195428 AU - Tepper JE TI - Adjuvant irradiation of gastrointestinal malignancies: impact on local control and tumor cure. AB - Radiation therapy has recently been used more frequently in the adjuvant treatment of gastrointestinal malignancies. A number of studies have shown a high local failure in patients with Stages B2 and C rectal carcinomas and in Stages B3, C2 and C3 colon carcinomas. In rectal cancer, both randomized and non-randomized studies have demonstrated improved local control and survival with the use of adjuvant radiation. Randomized studies have not been performed in colon cancer, but preliminary data from MGH indicate improved local control and survival in some patient subsets with the use of local irradiation after resection. Both gastric and pancreatic cancer have a greater propensity to distant metastases. A review of failure patterns after resection has, nonetheless, shown a high incidence of local recurrence and small prospective randomized studies have recently demonstrated a survival advantage with the use of adjuvant irradiation. MH - Clinical Trials ; Colonic Neoplasms/*RADIOTHERAPY/SURGERY ; Combined Modality Therapy ; Comparative Study ; Human ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Pancreatic Neoplasms/ *RADIOTHERAPY/SURGERY ; Prognosis ; Random Allocation ; Rectal Neoplasms/*RADIOTHERAPY/SURGERY ; Review ; Stomach Neoplasms/ *RADIOTHERAPY/SURGERY SO - Int J Radiat Oncol Biol Phys 1986 Apr;12(4):667-71 66 UI - 86191895 AU - Hoelzer KL ; Harrison BR ; Luedke SW ; Luedke DW TI - Vinblastine-associated pulmonary toxicity in patients receiving combination therapy with mitomycin and cisplatin. AB - Two of 33 patients entered in a local pilot study of mitomycin, vinblastine, and cisplatin for non-small cell lung cancer developed vinblastine-associated pulmonary toxicity. As with other reports of vinca alkaloid-related pulmonary toxicity, the regimen included mitomycin. Based on these cases and others previously reported, the incidence of abrupt pulmonary toxicity following vinca alkaloid administration as part of mitomycin/vinca alkaloid combination appears to be three to six percent. Suggestions for management are given. MH - Adenocarcinoma/DRUG THERAPY ; Aged ; Antineoplastic Agents, Combined/*ADVERSE EFFECTS/THERAPEUTIC USE ; Carcinoma, Squamous Cell/DRUG THERAPY ; Case Report ; Cisplatin/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Human ; Lung Neoplasms/DRUG THERAPY ; Male ; Middle Age ; Mitomycins/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Pilot Projects ; Pneumonia/*CHEMICALLY INDUCED ; Vinblastine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS SO - Drug Intell Clin Pharm 1986 Apr;20(4):287-9 67 UI - 86191491 AU - Adelstein DJ ; Tomashefski JF Jr ; Snow NJ ; Horrigan TP ; Hines JD TI - Mixed small cell and non-small cell lung cancer. AB - Seventeen (10 percent) of 176 patients with small-cell carcinoma of the lung seen at this hospital since 1976 proved to have mixed small-cell and non-small-cell tumors. The presence of a mixed lung cancer was established prior to chemotherapy or irradiation in nine patients. Eight were initially diagnosed as pure small-cell carcinoma but proved to have a mixed tumor at either surgery or autopsy. Of the 17 patients, eight received chemotherapy, and four had a partial response. Six of the 40 autopsies performed on patients with small-cell lung cancer demonstrated intrathoracic tumor which was histologically mixed. Extrathoracic metastases in these patients were heterogeneous and included pure small-cell, pure non-small-cell, and mixed histologic type. We conclude that mixed small-cell and non-small-cell lung cancers are relatively frequent and carry important prognostic and therapeutic implications. Clinical management of patients with small-cell lung cancer should therefore be flexible and tailored to the potential for histologic diversity. Mixed lung cancer in previously untreated patients suggests a common endodermal origin for small-cell and non-small-cell pulmonary tumors. MH - Adult ; Aged ; Biopsy ; Carcinoma, Oat Cell/*PATHOLOGY/THERAPY ; Female ; Human ; Lung/PATHOLOGY ; Lung Neoplasms/*PATHOLOGY/ THERAPY ; Male ; Middle Age ; Neoplasm Metastasis ; Neoplasms, Embryonal and Mixed/*PATHOLOGY/THERAPY ; Pneumonectomy SO - Chest 1986 May;89(5):699-704 68 UI - 86190981 AU - Mitchell DM ; Shah SH ; Edwards D ; Tobias JS ; Geddes DM ; Harper PG ; Souhami RL ; Spiro SG TI - Incidence of pulmonary nodules detected by computed tomography in patients with bronchial carcinoma. AB - Computed tomography (CT) is more sensitive in detecting pulmonary nodules than conventional chest radiography. The incidence of pulmonary nodules on thoracic CT scans, not visible on chest radiographs, in patients with small-cell carcinoma of the bronchus (SCCB) was 27%, and in patients with non-small-cell carcinoma (non-SCCB) the incidence was 28%. Some of these nodules may be malignant. This has implications for the surgical staging of patients with lung cancer in the United Kingdom, where there is a lower incidence of benign granulomatous nodules than in the USA. MH - Carcinoma, Bronchogenic/*PATHOLOGY ; Coin Lesion, Pulmonary/ PATHOLOGY/*RADIOGRAPHY ; Human ; Lung Neoplasms/*PATHOLOGY ; Support, Non-U.S. Gov't ; Tomography, X-Ray Computed SO - Clin Radiol 1986 Mar;37(2):151-2 69 UI - 86190292 AU - Stewart JA ; Ackerly CC ; Myers CF ; Newman RA ; Krakoff IH TI - Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728). AB - A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended. MH - Adult ; Aged ; Antineoplastic Agents/*ADVERSE EFFECTS/METABOLISM/ THERAPEUTIC USE ; Dermatitis Medicamentosa/ETIOLOGY ; Drug Evaluation ; Female ; Half-Life ; Human ; Kinetics ; Lung Neoplasms/DRUG THERAPY ; Male ; Middle Age ; Stomatitis/ CHEMICALLY INDUCED ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Thiadiazoles/*ADVERSE EFFECTS/METABOLISM/ THERAPEUTIC USE ; Uric Acid/BLOOD SO - Cancer Chemother Pharmacol 1986;16(3):287-91 70 UI - 86189671 AU - Thor A ; Ohuchi N ; Szpak CA ; Johnston WW ; Schlom J TI - Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3. AB - Murine monoclonal antibody B72.3, prepared against a membrane-enriched extract of human metastatic carcinoma, was reacted with a spectrum of adult and fetal human tissues using avidin-biotin-complex immunohistochemical techniques to evaluate the expression of the reactive tumor associated glycoprotein (TAG)-72 antigen. TAG-72 was shown to be expressed in several epithelial-derived cancers including 94% of colonic adenocarcinomas, 84% of invasive ductal carcinomas of the breast, 96% of non-small cell lung carcinomas, 100% of common epithelial ovarian carcinomas, as well as the majority of pancreatic, gastric, and esophageal cancers evaluated. TAG-72 expression was not observed, however, in tumors of neural, hematopoietic, or sarcomatous derivation, suggesting that the TAG-72 antigen is "pancarcinoma: in nature. Appreciable monoclonal antibody B72.3 reactivity was generally not observed in adult normal tissues, with limited reactivity noted in a few benign lesions of the breast and colon. TAG-72 antigen expression was detected, however, in fetal colon, stomach, and esophagus, thus defining TAG-72 as an oncofetal antigen. TAG-72 has previously been shown to be distinct from carcinoembryonic antigen and other tumor associated antigens. The pancarcinoma distribution and lack of significant reactivity with normal adult tissues of monoclonal antibody B72.3 suggest its potential diagnostic and therapeutic utility for human carcinomas. MH - Animal ; Antibodies, Monoclonal/*IMMUNOLOGY ; Antigens, Neoplasm/ *ANALYSIS ; Breast Neoplasms/IMMUNOLOGY ; Colonic Neoplasms/ IMMUNOLOGY ; Female ; Fetus/IMMUNOLOGY ; Glycoproteins/*ANALYSIS ; Histocytochemistry ; Human ; Immunoenzyme Technics ; Mice ; Neoplasms/DIAGNOSIS/*IMMUNOLOGY ; Pregnancy SO - Cancer Res 1986 Jun;46(6):3118-24 71 UI - 86189420 AU - Lyons MF ; Redmond J 3d ; Covelli H TI - Multiple primary neoplasia of the head and neck and lung. The changing histopathology. AB - The authors reviewed 1373 consecutive cases of patients with oral head and neck cancer or lung cancer and identified 25 patients with multiple primary neoplasia (MPN). All 25 MPN cases had squamous carcinoma of the head and neck; however, only 40% (N = 10) had squamous carcinoma of the lung. The histologic types of non-squamous lung carcinoma were: adenocarcinoma 36% (N = 9), small cell carcinoma 20% (N = 5), and large cell undifferentiated carcinoma 4% (N = 1). Of 927 cases of MPN of the head and neck and lung reported in the English language literature, only 100 cases (10.78%) demonstrated a histologic discrepancy between the primary tumors. Recent reports demonstrate a histologic shift toward non-squamous lung carcinoma in MPN that is similar to our data, and that corresponds to the increase in non-squamous carcinomas recently seen in lung cancer in general. Possible implications of these findings are discussed. MH - Adenocarcinoma/*PATHOLOGY ; Adult ; Aged ; Carcinoma, Squamous Cell/*PATHOLOGY ; Female ; Head and Neck Neoplasms/*PATHOLOGY ; Human ; Lung Neoplasms/*PATHOLOGY ; Male ; Middle Age ; *Neoplasms, Multiple Primary SO - Cancer 1986 Jun 1;57(11):2193-7 72 UI - 86181554 AU - de Jong WH ; Teppema JS ; Wagenaar SS ; Paques M ; Steerenberg PA ; Ruitenberg EJ TI - Histological evaluation of immunologically mediated tumor regression of the line 10 guinea pig hepatocarcinoma. AB - The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Gu:erin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with purulent lysis of the granulomatous tissue, was observed. Specific immune-mediated tumor rejection occurred in animals both after active immunization and after adoptive transfer of immune spleen cells. In actively immunized animals the tumor cells were rapidly rejected and from day 4 onwards no tumor cells could be detected at the injection site. Lymphocytes were the major component of the inflammatory reaction; large mononuclear cells were present to a lesser extent and basophilic granulocytes were regularly observed. After adoptive transfer of immunity with immune spleen cells given simultaneously with an intradermal innoculation of tumor cells, an essentially similar rejection reaction was found, although tumor cell rejection was delayed. Lymphocytes and large mononuclear cells were found in equal proportions, whereas basophilic granulocytes were always present in smaller numbers. After BCG-induced regression and in adoptively transferred immune rejection, a fibroblast component was more prominent than in untreated control tumors. This reaction tended to isolate smaller tumor cell areas into islets of decreasing sizes. In contrast with the fibroblast component of growing tumors, the proliferative pre-existing fibrous tissue in tumors undergoing regression or rejection showed a loosely arranged architecture and contained a marked cellular infiltrate. From the results of the present study it was concluded that the morphological expression of line 10 tumor rejection varies. Without immune cells, BCG is needed for the induction of a local inflammatory reaction, which was granulomatous in type and eventually led to complete tumor cell eradication.(ABSTRACT TRUNCATED AT 400 WORDS) MH - Animal ; Female ; Graft Rejection ; Guinea Pigs ; Immunization ; Immunization, Passive ; Immunotherapy ; Inflammation/PATHOLOGY ; Liver Neoplasms, Experimental/PATHOLOGY/*THERAPY ; Lymphocytes/ PATHOLOGY ; Mycobacterium Bovis/IMMUNOLOGY ; Neoplasm Transplantation ; Review ; Spleen/IMMUNOLOGY ; Support, Non-U.S. Gov't ; Transplantation, Isogeneic SO - Virchows Arch [B] 1986;50(3):249-69 73 UI - 86175485 AU - Patchell RA ; Cirrincione C ; Thaler HT ; Galicich JH ; Kim JH ; Posner JB TI - Single brain metastases: surgery plus radiation or radiation alone. AB - We reviewed the records of patients treated for single brain metastases from non-small-cell lung cancer for 1978 through 1982. Forty-three patients received surgical treatment, including 37 who had surgery plus postoperative whole-brain radiation therapy and 6 patients who had surgery after failing to respond to radiation therapy. The surgically treated patients were matched with 43 patients treated with radiation therapy alone. The combined therapy group had significantly longer survivals than those treated with radiation therapy alone (19 months versus 9 months). The rates of local recurrence and neurologically related deaths were significantly higher in the radiation therapy-alone group. Patients treated with combined therapy survived longer, and the increased survival was due to lower recurrence of brain metastases after surgery and fewer neurologically related deaths. MH - Adenocarcinoma/RADIOTHERAPY/*SECONDARY/SURGERY ; Adult ; Aged ; Brain Neoplasms/RADIOTHERAPY/*SECONDARY/SURGERY ; Carcinoma/ RADIOTHERAPY/*SECONDARY/SURGERY ; Carcinoma, Oat Cell/ RADIOTHERAPY/*SECONDARY/SURGERY ; Female ; Human ; Lung Neoplasms/ THERAPY ; Male ; Middle Age SO - Neurology 1986 Apr;36(4):447-53 74 UI - 86167677 AU - Schaake-Koning C ; Bartelink H ; Adema BH ; Schuster-Uitterhoeve L ; van Zandwijk N TI - Radiotherapy and cis-diammine dichloroplatinum (II) as a combined treatment modality for inoperable non-small cell lung cancer: a dose finding study. AB - A dose finding study was carried out to establish the dose of cis-diammine dichloroplatinum (II), cDDP, that can be combined with high dose radiotherapy routinely in patients with inoperable non-small cell lung cancer. The patients were irradiated over a period of 2 weeks, 5 fractions a week, followed by a rest period of 14 days. Thereafter a second course of 2 weeks was given; a total dose of 55 Gy was achieved. The weekly cDDP administration in a 3 hour infusion with pre- and posthydration preceded the first day irradiation. Twenty patients were evaluable for acute toxicity. The dose limiting factor appeared to be severe nausea and vomiting, which was not responsive to anti-emetic therapy at a cDDP level of 35 mg/m2. No renal or significant hematological side effects were observed. Complete response was seen in 10 patients, using X rays and CT scans; this was confirmed by bronchoscopy with biopsies in 9 patients. Partial remission was scored in 7 patients and no change in 4 patients. cDDP as a radiosensitizer will be further studied at a dose level of 30 mg/m2 a week or 6 mg/m2 a day in a prospective, randomized EORTC Phase II study. MH - Adenocarcinoma/DRUG THERAPY/RADIOTHERAPY ; Adult ; Aged ; Carcinoma, Squamous Cell/DRUG THERAPY/RADIOTHERAPY ; Cisplatin/ *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/DRUG THERAPY/ *RADIOTHERAPY ; Male ; Middle Age ; Radiation-Sensitizing Agents/ *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Radiotherapy, High Energy SO - Int J Radiat Oncol Biol Phys 1986 Mar;12(3):379-83 75 UI - 86163521 AU - Klastersky J ; Sculier JP TI - Nonsurgical combined modality therapies in non-small cell lung cancer. AB - Nonsurgical combined approaches of non-small cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs. MH - Antineoplastic Agents/THERAPEUTIC USE ; Antineoplastic Agents, Combined/THERAPEUTIC USE ; Carcinoma/DRUG THERAPY/RADIOTHERAPY/ *THERAPY ; Combined Modality Therapy ; Human ; Lung Neoplasms/ DRUG THERAPY/RADIOTHERAPY/*THERAPY ; Radiation Dosage ; Review SO - Chest 1986 Apr;89(4 Suppl):289S-294S 76 UI - 86163520 AU - Cox JD TI - Non-small cell lung cancer. Role of radiation therapy. AB - The most important role of radiation therapy for carcinoma of the lung is its contribution to cure. Important technical advances in radiation therapy have been made that, along with advances in understanding the natural history of cancer of the lung, permit treatment with a higher expectation of cure than previously. Studies of fractionation have defined the doses required for control of intrathoracic tumors, and ancillary studies have better defined the treatment volumes necessary. Operable patients benefit from postoperative irradiation only when there is involvement of regional lymph nodes. In inoperable cases, the greatest survival benefit from radiation therapy is found among those who have a high performance status. Patients with adenocarcinoma and large cell carcinoma have a greater probability of long-term survival than those with squamous carcinoma. Investigations of altered fractionation may lead to improved results in radiation therapy for all histopathologic types of carcinoma of the lung. MH - Adenocarcinoma/MORTALITY/*RADIOTHERAPY/SURGERY ; Brain Neoplasms/ RADIOTHERAPY/SECONDARY ; Carcinoma, Oat Cell/MORTALITY/ RADIOTHERAPY/SURGERY ; Carcinoma, Squamous Cell/MORTALITY/ *RADIOTHERAPY/SURGERY ; Human ; Longevity ; Lung Neoplasms/ MORTALITY/*RADIOTHERAPY/SURGERY ; Review ; Time Factors SO - Chest 1986 Apr;89(4 Suppl):284S-288S 77 UI - 86163519 AU - Gazdar AF TI - Advances in the biology of non-small cell lung cancer. AB - We have initiated an in-depth, comprehensive study of non-SCLC in the expectation that improvements in clinical management and diagnosis of lung cancer patients will follow. We have established and characterized over 30 such tumors in long-term culture and as xenografts in athymic nude mice. These models usually retain the morphologic and other properties of the tumors from which they were derived. With the use of fully defined medium, most SCLC and adenocarcinomas can be established as long-term cultures. The growth conditions for squamous cell carcinomas have not been fully defined, and the success rate is low. In contrast to SCLC, there is considerable heterogeneity of non-SCLC tumors, with more than 12 phenotypes identified among the first 30 lines established. In addition, there is considerable overlap of properties, both within the non-SCLC types as well as between non-SCLC and SCLC. These findings indicate a common origin for all lung cancers. Radiation and drug sensitivity studies suggest that cell line data may correlate with clinical responses. Clinical protocols utilizing our ability to culture and drug test individual tumors are currently under way. They represent the first steps in a combined clinico-laboratory approach to the management of lung cancer. MH - Adenocarcinoma/CLASSIFICATION/*PATHOLOGY ; Animal ; Carcinoma, Oat Cell/CLASSIFICATION/PATHOLOGY ; Carcinoma, Squamous Cell/ CLASSIFICATION/*PATHOLOGY ; Cell Division ; Cell Line ; DNA, Neoplasm/ANALYSIS ; Epidermal Growth Factor-Urogastrone/ METABOLISM ; Human ; Lung Neoplasms/CLASSIFICATION/*PATHOLOGY ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Ploidies ; Transplantation, Heterologous SO - Chest 1986 Apr;89(4 Suppl):277S-283S 78 UI - 86162754 AU - Qasim M TI - Systemic radiation and split-course radiotherapy for non-small-cell bronchial carcinoma. AB - One hundred and thirty-eight patients with inoperable non-small-cell bronchial carcinoma, Stage III, have been treated with systemic radiation and radical radiotherapy by a split-course technique. Systemic radiation has been used as an adjuvant therapy to deal with micrometastases or subclinical disease. A historical comparison has been made with a similar group of patients treated radically by split-course radiotherapy alone. It is shown that the incidence of distant metastases has decreased and the disease-free survival rate has improved. There were 26% of patients who survived 4 years disease-free, as compared with 7% in the group where no systemic radiation therapy was given. In view of a higher incidence of brain metastases and radiation pneumonitis, the technique and dosage of systemic radiation therapy have been modified. MH - Adenocarcinoma/MORTALITY/RADIOTHERAPY ; Aged ; Carcinoma, Bronchogenic/MORTALITY/*RADIOTHERAPY ; Carcinoma, Squamous Cell/ MORTALITY/RADIOTHERAPY ; Human ; Lung Neoplasms/MORTALITY/ *RADIOTHERAPY ; Radiotherapy Dosage SO - Clin Radiol 1986 Jan;37(1):51-3 79 UI - 86161451 AU - Hainsworth JD ; Porter LL 3d ; Johnson DH ; Hande KR ; Wolff SN ; Birch R ; Enas G ; Greco FA TI - Combination chemotherapy with vindesine, etoposide, and cisplatin in non-small cell lung cancer: a pilot study of the Southeastern Cancer Study Group. AB - Ninety-two patients with advanced non-small cell lung cancer were treated with a combination chemotherapy regimen containing cisplatin, vindesine, and etoposide. Eighteen patients (20%) achieved major responses to therapy (three complete responders and 15 partial responders). Response rates were similar in each histologic subtype. Initial performance status was an important determinant of response; 42% of the patients with a Karnofsky performance status greater than or equal to 70% responded versus 5% of those with a performance status less than 50%. The median duration of partial response was 21 weeks; complete responders had a median response duration of 50 weeks. The median survival for the entire group was 23.5 weeks. Toxicity with this regimen was acceptable; myelosuppression was the major toxic effect and was severe in only 10% of the patients. This regimen produced response rates comparable to those reported with other combinations containing cisplatin. Survival advantage in patients receiving this treatment is not established. MH - Adenocarcinoma/DRUG THERAPY ; Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/*THERAPEUTIC USE ; Bone Marrow/ DRUG EFFECTS ; Carcinoma/DRUG THERAPY ; Carcinoma, Squamous Cell/ DRUG THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE ; Etoposide/ ADMINISTRATION & DOSAGE ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY/MORTALITY ; Male ; Middle Age ; Pilot Projects ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Vindesine/ ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Mar;70(3):339-41 80 UI - 86161450 AU - Blum RH ; Cooper J ; Schmidt AM ; Ashinoff R ; Collins A ; Wernz JC ; Speyer JL ; Boyd A ; Muggia FM TI - Cisplatin and vinblastine chemotherapy for metastatic non-small cell carcinoma followed by irradiation in patients with regional disease. AB - Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Carcinoma/MORTALITY/*THERAPY ; Cisplatin/ ADMINISTRATION & DOSAGE ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/MORTALITY/*THERAPY ; Male ; Middle Age ; Neoplasm Metastasis ; Radiotherapy/ADVERSE EFFECTS ; Radiotherapy Dosage ; Support, U.S. Gov't, P.H.S. ; Vinblastine/ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Mar;70(3):333-7 81 UI - 86161332 AU - Scheithauer W ; Von Hoff DD ; Forseth B ; Cowan JD TI - Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay. AB - The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials. MH - Antineoplastic Agents/PHARMACODYNAMICS ; *Colony-Forming Units Assay ; Dose-Response Relationship, Drug ; Female ; Human ; Male ; Misonidazole/*PHARMACODYNAMICS ; Oxygen ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; *Tumor Stem Cell Assay SO - Cancer Drug Deliv 1986 Winter;3(1):15-24 82 UI - 86145584 AU - Ferguson MK ; Little AG ; Golomb HM ; Hoffman PC ; DeMeester TR ; Beveridge R ; Skinner DB TI - The role of adjuvant therapy after resection of T1 N1 M0 and T2 N1 M0 non-small cell lung cancer. AB - Thirty-four consecutive patients with non-small cell lung cancer plus N1 nodal metastases (eight with T1 N1 M0 and 26 with T2 N1 M0) were retrospectively reviewed. Nineteen had adenocarcinoma, 11 had squamous disease, and four had large cell carcinoma. Eleven patients had surgical resection alone (32.3%), with a median survival of 13 months. Seven patients (20.6%) had resection followed by radiation therapy, with a median survival of 19.2 months. Sixteen patients (47.1%) had resection followed by radiation therapy and chemotherapy, consisting of cyclophosphamide, doxorubicin, methotrexate, and procarbazine. Median survival for the latter group was 45.5 months, significantly greater than for those treated with resection alone (p less than 0.005). We did not observe any relationship between survival and age, cell type, number or location of diseased hilar nodes, distance of tumor from the resected bronchial margin, tumor size, the presence or absence of visceral pleural involvement, or the type of resection performed. Resection in combination with adjuvant radiation therapy and chemotherapy offers improved median survival over resection alone in patients with T1 N1 M0 and T2 N1 M0 non-small cell lung cancer. MH - Adenocarcinoma/DRUG THERAPY/MORTALITY/RADIOTHERAPY/*SURGERY ; Adult ; Aged ; Carcinoma, Oat Cell/DRUG THERAPY/MORTALITY/ RADIOTHERAPY/*SURGERY ; Carcinoma, Squamous Cell/DRUG THERAPY/ MORTALITY/RADIOTHERAPY/*SURGERY ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/DRUG THERAPY/MORTALITY/ RADIOTHERAPY/*SURGERY ; Lymphatic Metastasis ; Male ; Middle Age ; Neoplasm Recurrence, Local ; Probability ; Retrospective Studies SO - J Thorac Cardiovasc Surg 1986 Mar;91(3):344-9 83 UI - 86139401 AU - Majid OA ; Lee S ; Khushalani S ; Seydel HG TI - The response of atelectasis from lung cancer to radiation therapy. AB - Between January 1981 and June 1983, 33 newly diagnosed patients with lung cancer presented with radiological findings of atelectasis. These patients were treated by primary radiation therapy, with doses ranging from 1200 to 6000 cGy. The response of atelectasis to radiation therapy was established on the basis of follow-up chest roentgenograms. Of the 28 patients with non-small cell carcinoma of lung, there were 17 (61%) who had improvement of the atelectasis. Among these, 13 patients were treated with doses ranging from 5000 to 6000 cGy in 5 to 8 weeks; 9 of these (70%) responded. By histological subtype, the numbers, though small, show that three of eight patients with adenocarcinoma responded, as compared to 2 out of 4 with large cell undifferentiated carcinoma and 12 of 16 patients with squamous cell carcinoma. In patients treated by more than 5000 cGy, four of eight (50%) patients with squamous cell carcinoma had a complete response and three (37.5%) had a partial relief of atelectasis, for a total response of 87.5%. The study indicates the importance of radiation therapy in the management of atelectasis caused by primary lung cancer. MH - Adenocarcinoma/COMPLICATIONS/RADIOTHERAPY ; Atelectasis/ETIOLOGY/ *RADIOTHERAPY ; Carcinoma/*COMPLICATIONS/RADIOTHERAPY ; Carcinoma, Oat Cell/COMPLICATIONS/RADIOTHERAPY ; Carcinoma, Squamous Cell/COMPLICATIONS/RADIOTHERAPY ; Human ; Lung Neoplasms/ *COMPLICATIONS/RADIOTHERAPY SO - Int J Radiat Oncol Biol Phys 1986 Feb;12(2):231-2 84 UI - 86133362 AU - Huberman M ; Lokich J ; Greene R ; Paul S ; Phillips D ; Sonneborn H ; Zipoli T TI - Vinblastine plus cisplatin in advanced non-small cell lung cancer: lack of advantage for vinblastine infusion schedule. AB - We have evaluated 31 patients with advanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete responses. Although five of nine (55%) of the responders were alive at greater than or equal to 1 year, three of the 31 patients experienced drug-related mortality. Our experience, as well as a review of previously reported trials in the literature, suggests that the infusion schedule of vinblastine offers no advantage over the bolus schedule. MH - Adenocarcinoma/DRUG THERAPY ; Adolescence ; Adult ; Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Carcinoma, Oat Cell/DRUG THERAPY ; Carcinoma, Squamous Cell/DRUG THERAPY ; Cisplatin/ADMINISTRATION & DOSAGE ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Vinblastine/ ADMINISTRATION & DOSAGE SO - Cancer Treat Rep 1986 Feb;70(2):287-9 85 UI - 86133260 AU - Luk GD ; Baylin SB TI - Anchorage dependency effects on difluoromethylornithine cytotoxicity in human lung carcinoma cells. AB - Difluoromethylornithine (DFMO), a specific, irreversible, enzyme-activated inhibitor of ornithine decarboxylase activity, the first and rate-limiting step in polyamine biosynthesis, has been shown to inhibit neoplastic cell proliferation in culture. In most cases, such inhibition is not accompanied by cell loss, with the exception of multiple cell lines of human small cell lung carcinoma (SCC), a human leukemia cell line (HL-60), and possibly the B16 melanoma cell line. The first two cell types grow as anchorage-independent suspension cultures, the HL-60 as single cells and the SCC as multicellular spheroid aggregates. Moreover, in the spectrum of human lung carcinoma cells in culture, the SCC cells respond in a cytotoxic manner to DFMO, whereas the non-small cell lung carcinoma (non-SCC) cells, which are anchorage dependent, show only growth inhibition, without actual cell loss. In the present study, we have investigated relationships between anchorage-dependent and -independent growth patterns of cells in culture and their response to DFMO treatment. Two non-SCC lung cancer cell lines, which normally grow as anchorage-dependent monolayers, show growth inhibition but no cell loss with the addition of DFMO. When these anchorage-dependent cells were forced to grow as multicellular aggregates, by coating the culture flask with Teflon, the cells developed an increased sensitivity to DFMO. They showed not only inhibition of cell proliferation but also cell death. Two SCC cell lines, which normally grow as anchorage-independent spheroids, developed adherence to the culture dishes coated with fibronectin. These cells, which show a cytotoxic response to DFMO during normal anchorage-independent growth, developed a decreased sensitivity to DFMO, showing only cell growth inhibition, but no cell death when treated during anchorage-dependent growth. Our data thus suggest that the state of anchorage dependence of lung cancer cells in culture is a critical factor in determining their response to polyamine depletion during treatment with DFMO. MH - Carcinoma, Oat Cell/PATHOLOGY ; Carcinoma, Squamous Cell/ PATHOLOGY ; Cell Aggregation ; Cell Communication ; Cell Survival/ DRUG EFFECTS ; Cells, Cultured ; Cytoskeleton/DRUG EFFECTS ; Human ; Lung Neoplasms/DRUG THERAPY/*PATHOLOGY ; Ornithine/ *ANALOGS & DERIVATIVES/PHARMACODYNAMICS/THERAPEUTIC USE ; Polyamines/BIOSYNTHESIS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Apr;46(4 Pt 1):1844-8 86 UI - 86130732 AU - Falzon M ; McMahon JB ; Schuller HM TI - Xenobiotic-metabolizing enzyme activity in human non-small-cell derived lung cancer cell lines. AB - Human lung cancer cell lines in culture were investigated for the expression of monooxygenase and other xenobiotic-metabolizing enzyme activities. Two bronchiolo-alveolar carcinoma derived cell lines (NCI-H322 and NCI-H358) and two small-cell carcinoma derived cell lines (NCI-H128 and NCI-H69) were used. Previous work has shown that NCI-H322 has ultrastructural features of Clara cells while NCI-H358 shows characteristics of alveolar type II cells [Schuller et al., Proc. Am. Ass. Cancer Res. 26, 27 (1985)]. NCI-H128 and NCI-H69 show very poor differentiation of cytoplasmic organelles. Cytochrome P-450 levels were spectroscopically detectable only in NCI-H322. Both NCI-H322 and NCI-H358, but not NCI-H69 and NCI-H128, exhibited aryl hydrocarbon hydroxylase (using benzo[a] pyrene as substrate) and ethoxycoumarin O-deethylase activities. These activities were highly inducible following pretreatment with the polycyclic aromatic hydrocarbons (PAH) beta-naphthoflavone or benzo[a] anthracene. The PAH produced a 2-fold increase in spectroscopically detectable cytochrome P-450 levels in NCI-H322. Following induction, cytochrome P-450 was also spectroscopically detectable in NCI-H358. No aldrin epoxidase activity was present in either untreated or pretreated cell lines. Pretreatment with phenobarbitone or dexamethasone did not induce the aryl hydrocarbon hydroxylase activity in either NCI-H322 or NCI-H358. The ethoxycoumarin O-deethylase activity in beta-naphthoflavone-pretreated NCI-H322 and NCI-H358 was inhibited in a concentration-dependent manner by ellipticine, alpha-naphthoflavone, cimetidine or metyrapone. Untreated NCI-H322 and NCI-H358 also contained cytochrome b5, NADPH cytochrome c reductase and epoxide hydrolase activities. None of these enzyme activities measured was detectable in the untreated or pretreated small-cell derived cancer cell lines (NCI-H128 and NCI-H69). These data show that the two bronchiolo-alveolar carcinoma derived cell lines (NCI-H322 and NCI-H358) exhibit cytochrome P-448-dependent monooxygenase activity and may thus prove useful to study the processes of xenobiotic activation in human lung. MH - Aryl Hydrocarbon Hydroxylases/METABOLISM ; Carcinoma, Bronchiolar/ *ENZYMOLOGY ; Carcinoma, Oat Cell/ENZYMOLOGY ; Cell Line ; Cytochromes/METABOLISM ; Human ; Lung Neoplasms/*ENZYMOLOGY ; Mixed Function Oxidases/*METABOLISM ; Oxygenases/ANTAGONISTS & INHIBITORS/METABOLISM ; Substrate Specificity SO - Biochem Pharmacol 1986 Feb 15;35(4):563-8 87 UI - 86130533 AU - Casero RA Jr ; Baylin SB ; Nelkin BD ; Luk GD TI - Human lung tumor sensitivity to difluoromethylornithine as related to ornithine decarboxylase messenger RNA levels. AB - The differential response to polyamine depletion has been studied in two types of human lung tumor cells. Small cell lung carcinoma cells die following polyamine depletion by difluoromethylornithine treatment while non-small cell lines demonstrate a typical cytostatic response. We now report that a small cell line, NCI H82, has a lower apparent capacity for polyamine biosynthesis than does a representative non-small cell, NCI H157. In subconfluent cultures, the ornithine decarboxylase activity is 25 times lower in the small cell than the non-small cell and by comparison, the polyamines in the small cell line are markedly reduced. Most significantly, levels of mRNA coding for ornithine decarboxylase are approximately 100-fold lower in the small cell than the non-small cell line, and this difference does not appear to be a result of gene rearrangement. These results suggest that differential sensitivity to polyamine depletion is related to different steady-state levels of ornithine decarboxylase mRNA. MH - Carcinoma/ENZYMOLOGY/FAMILIAL & GENETIC/PATHOLOGY ; Carcinoma, Oat Cell/ENZYMOLOGY/FAMILIAL & GENETIC/PATHOLOGY ; Cell Cycle/ DRUG EFFECTS ; Cells, Cultured ; Human ; Lung Neoplasms/ ENZYMOLOGY/FAMILIAL & GENETIC/PATHOLOGY ; Ornithine/*ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Ornithine Decarboxylase/*GENETICS ; Polyamines/METABOLISM ; Putrescine/PHARMACODYNAMICS ; RNA, Messenger/METABOLISM ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Biochem Biophys Res Commun 1986 Jan 29;134(2):572-9 88 UI - 86107501 AU - Quinn DL ; Ostrow LB ; Porter DK ; Shelton DK Jr ; Jackson DE Jr TI - Staging of non-small cell bronchogenic carcinoma. Relationship of the clinical evaluation to organ scans. AB - Organ scans are generally performed on patients with bronchogenic carcinoma only when clinical evaluation is suspicious for metastases. However, it is not clear whether the clinical abnormalities will direct attention to the single organ which should be scanned, or if all three organs (bone, brain, liver) should be evaluated if any clinical abnormality is present. We investigated the use of triple organ radionuclide scanning and computerized tomography (CT) of the brain in the initial staging of patients with non-small cell bronchogenic carcinoma with no obvious metastases. Of 122 patients with newly diagnosed lung cancer, 53 met our criteria for further study. Thirty-three (62 percent) of these had at least one clinical abnormality suggestive of metastasis. Bone scanning detected metastases in seven (21 percent) and head CT in two additional patients (6 percent). Brain and liver scanning had no yield. In only five of these nine patients did the clinical abnormality direct attention to the organ with detectable metastases. Twenty of the 53 (38 percent) patients had a negative routine clinical evaluation, yet bone scanning showed metastases in three (15 percent). We concluded that clinical abnormalities are not specific for the organ in which metastases may be detected, so three scans (bone, liver, CT of the brain) should be obtained if there is any suspicion of metastasis based on history, physical examination, and laboratory tests. The value of bone scanning in clinically normal patients deserves further study. MH - Adult ; Aged ; Bone and Bones/*RADIONUCLIDE IMAGING ; Bone Neoplasms/RADIONUCLIDE IMAGING/SECONDARY ; Brain/*RADIONUCLIDE IMAGING ; Brain Neoplasms/RADIONUCLIDE IMAGING/SECONDARY ; Carcinoma, Bronchogenic/*PATHOLOGY/RADIONUCLIDE IMAGING/SECONDARY ; Female ; Human ; Liver/*RADIONUCLIDE IMAGING ; Liver Neoplasms/ RADIONUCLIDE IMAGING/SECONDARY ; Lung Neoplasms/*PATHOLOGY ; Male ; Middle Age ; Neoplasm Staging/METHODS SO - Chest 1986 Feb;89(2):270-5 89 UI - 86105662 AU - Takita H ; Regal AM ; Antkowiak JG ; Rao UN ; Botsoglou NK ; Lane WW TI - Chemotherapy followed by lung resection in inoperable non-small cell lung carcinomas due to locally far-advanced disease. AB - From 1977, 29 patients with inoperable non-small cell lung carcinoma due to locally far-advanced disease underwent lung resection after receiving two to eight courses of chemotherapy. After the surgery was performed, three additional courses of chemotherapy were given. The overall median survival from onset of the chemotherapy was 30.5 months; postoperatively, it was 24.5 months (five patients survived greater than 5 years). Postoperative mortality was 10.3%. The overall survival results compare favorably with those obtained with radiation therapy. MH - Adult ; Aged ; Antineoplastic Agents/ADMINISTRATION & DOSAGE ; Case Report ; Combined Modality Therapy ; Female ; Human ; Lung Neoplasms/MORTALITY/*THERAPY ; Male ; Middle Age ; *Pneumonectomy SO - Cancer 1986 Feb 1;57(3):630-5 90 UI - 86105610 AU - Sato T ; Mukai M ; Ando N ; Tashiro Y ; Iri H ; Abe O ; Watanabe Y TI - Small cell carcinoma (non-oat cell type) of the esophagus concomitant with invasive squamous cell carcinoma and carcinoma in situ. A case report. AB - A case of double primary invasive carcinoma of the esophagus, consisting of well-differentiated squamous cell carcinoma and non-oat cell small cell carcinoma without squamous differentiation, is presented. This is the first reported case of a double or multiple primary invasive carcinoma of the esophagus in which one component is small cell carcinoma (oat cell or non-oat cell). Furthermore, the mucosal epithelium around the non-oat cell small cell carcinoma revealed multiple dysplasia and carcinoma in situ. These lesions were definitely separated from the invasive carcinoma and from each other. The results suggest that pure non-oat cell small cell carcinoma of the esophagus without squamous differentiation is derived from the esophageal squamous epithelium, and is a variant of squamous cell carcinoma. MH - Aged ; Carcinoma in Situ/*PATHOLOGY ; Carcinoma, Oat Cell/ PATHOLOGY ; Carcinoma, Squamous Cell/*PATHOLOGY ; Case Report ; Esophageal Neoplasms/*PATHOLOGY ; Histocytochemistry ; Human ; Male ; Neoplasms, Multiple Primary/*PATHOLOGY SO - Cancer 1986 Jan 15;57(2):328-32 91 UI - 86100174 AU - Heavey LR ; Glazer GM ; Gross BH ; Francis IR ; Orringer MB TI - The role of CT in staging radiographic T1N0M0 lung cancer. AB - Thirty-one patients with non-small-cell bronchogenic carcinoma and standard chest radiographs showing T1N0M0 tumors underwent preoperative chest and upper abdominal computed tomography (CT) with subsequent thorough surgical-pathologic correlation of their disease status. Eight patients (25.8%) had tissue-proven mediastinal or distant metastasis at presentation. In five (62.5%) of these eight patients the presence of unresectable disease was detected by CT and an unnecessary thoracotomy was avoided. These five patients comprised three with mediastinal lymph-node metastasis, one with adrenal metastasis, and one with a coexistent contralateral, proximal endobronchial tumor. Three patients with unresectable disease not detected by CT (CT false negatives) had metastasis to normal-sized mediastinal lymph nodes. There were two CT false-positive diagnoses of adrenal metastasis in patients proven by CT-guided aspiration to have benign adrenal masses, and these patients subsequently underwent curative lung resection. Although the data base is relatively small, the authors conclude that preoperative CT may be useful in evaluating patients with radiographic T1N0M0 lung cancer. MH - Adenocarcinoma/PATHOLOGY/RADIOGRAPHY ; Aged ; Carcinoma, Bronchogenic/*PATHOLOGY/RADIOGRAPHY ; Carcinoma, Squamous Cell/ PATHOLOGY/RADIOGRAPHY ; Female ; Human ; Lung Neoplasms/ *PATHOLOGY/RADIOGRAPHY ; Male ; Middle Age ; Neoplasm Staging ; Support, Non-U.S. Gov't ; *Tomography, X-Ray Computed SO - AJR 1986 Feb;146(2):285-90 92 UI - 86088040 AU - Ruckdeschel JC ; Finkelstein DM ; Ettinger DS ; Creech RH ; Mason BA ; Joss RA ; Vogl S TI - A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. AB - Between October 1981 and June 1983, the Eastern Cooperative Oncology Group (ECOG) conducted a prospectively randomized trial (EST 1581) of the four most active chemotherapy regimens for metastatic non-small-cell lung cancer (NSCLC). Four hundred eighty-six good performance status patients (PS 0 or 1; 81%) were randomized to receive cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); mitomycin, vinblastine, and cisplatin (MVP); etoposide and cisplatin (VP-P); or vindesine and cisplatin (VDA-P). All regimens were administered in the doses and schedules originally reported. Complete response (CR) plus partial response (PR) rates for the four regimens were CAMP, 17%; MVP, 31%; VP-P, 20%; and VDA-P, 25%. The response rate for MVP was significantly higher in patients with squamous and adenocarcinoma histologies, but there was no impact on median survival (overall, 24.5 weeks). The duration of response did not differ by treatment as previously suggested for VDA-P. There were 15 CRs (CAMP, one; MVP, six; VP-P, two; VDA-P, six), and 12 patients have survived more than 2 years. Toxicity was significant with 20 treatment-related deaths. CAMP was significantly less toxic than the other regimens (P less than .001). VDA-P demonstrated significantly more life-threatening (seven) and lethal (three) episodes of nephrotoxicity (P less than .001) despite an aggressive hydration program that in itself caused significant morbidity. Analysis of the toxicity data showed, however, that most of the severe toxicity occurred in the 19% of patients who were initially PS 2, suggesting that they are not appropriate candidates for trials of new agents or combinations. None of these regimens can be recommended as a standard therapy for metastatic NSCLC. MH - Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Cisplatin/ADMINISTRATION & DOSAGE ; Clinical Trials ; Comparative Study ; Cyclophosphamide/ADMINISTRATION & DOSAGE ; Doxorubicin/ ADMINISTRATION & DOSAGE ; Etoposide/ADMINISTRATION & DOSAGE ; Female ; Follow-Up Studies ; Human ; Lung Neoplasms/*DRUG THERAPY/ PATHOLOGY ; Male ; Methotrexate/ADMINISTRATION & DOSAGE ; Middle Age ; Mitomycins/ADMINISTRATION & DOSAGE ; Neoplasm Metastasis ; Procarbazine/ADMINISTRATION & DOSAGE ; Progesterone/ ADMINISTRATION & DOSAGE ; Random Allocation ; Support, U.S. Gov't, P.H.S. ; Vinblastine/ADMINISTRATION & DOSAGE ; Vindesine/ ADMINISTRATION & DOSAGE SO - J Clin Oncol 1986 Jan;4(1):14-22 93 UI - 86079177 AU - Brower M ; Carney DN ; Oie HK ; Gazdar AF ; Minna JD TI - Growth of cell lines and clinical specimens of human non-small cell lung cancer in a serum-free defined medium. AB - We tested the ability of serum-free media to support the in vitro growth of human non-small cell lung carcinoma. A medium containing insulin, transferrin, sodium selenite, hydrocortisone, epidermal growth factor, and bovine serum albumin (1 mg/ml) with serum precoating of culture dishes (modified LA medium) supported three previously established cell lines of non-small cell lung cancer and prevented fibroblast proliferation in fresh tumor specimens but did not support long term tumor cell growth from fresh specimens. We added triiodothyronine, sodium pyruvate, and additional glutamine, insulin, and epidermal growth factor to modified LA medium, precoated with fibronectin and collagen instead of serum, and deleted bovine serum albumin, defining a new medium called ACL-3. ACL-3 medium alone supported the short term growth of 10 of 12 cell lines and the soft agarose cloning of 9 of 12 cell lines tested, and ACL-3 supplemented by an optimal concentration of bovine serum albumin (5 mg/ml) supported the long term growth of 10 of 12 cell lines tested. Moreover, we have grown tumor cells for more than 6 months from 11 of 33 (33%) consecutive fresh clinical specimens of human lung adenocarcinoma in ACL-3 with bovine serum albumin. ACL-3 medium provides a defined environment for the study of growth factor requirements of human non-small cell lung cancer and enhances our ability to grow human lung cancer, particularly adenocarcinoma, in vitro. MH - Adenocarcinoma/*PATHOLOGY ; Carcinoma, Squamous Cell/PATHOLOGY ; Cell Division/DRUG EFFECTS ; Cell Line ; *Culture Media ; Extracellular Matrix/PHYSIOLOGY ; Growth Substances/ PHARMACODYNAMICS ; Human ; Lung Neoplasms/*PATHOLOGY ; Sepharose ; Tissue Culture SO - Cancer Res 1986 Feb;46(2):798-806 94 UI - 86079063 AU - Bitran JD ; Golomb HM ; Hoffman PC ; Albain K ; Evans R ; Little AG ; Purl S ; Skosey C TI - Protochemotherapy in non-small cell lung carcinoma. An attempt to increase surgical resectability and survival. A preliminary report [published erratum appears in Cancer 1986 Sep 15;58(6):1377] AB - Twenty patients with Stage IIIM0 (T3N2) non-small cell lung cancer were treated with vindesine, etoposide, and Platinol (cisplatin) (ELETOP) chemotherapy in an attempt to decrease tumor size and increase resectability and survival. ELETOP chemotherapy induced a 70% response rate (all partial responses) within 6 weeks, and three patients were able to undergo curative resection. Toxicities with ELETOP were moderately severe, with leukocyte and platelet nadirs on day 15. This pilot study demonstrates the feasibility of protochemotherapy in non-small cell lung cancer. MH - Adult ; Aged ; Antineoplastic Agents, Combined/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Cisplatin/ADVERSE EFFECTS/THERAPEUTIC USE ; Etoposide/ADVERSE EFFECTS/THERAPEUTIC USE ; Female ; Human ; Lung Neoplasms/*DRUG THERAPY/MORTALITY/SURGERY ; Male ; Middle Age ; Support, Non-U.S. Gov't ; Vindesine/ADVERSE EFFECTS/THERAPEUTIC USE SO - Cancer 1986 Jan 1;57(1):44-53