==================================CMR49================================== 49. Looking at eye and brain toxicity after the intra-carotid injection of drugs, usually BCNU, for the treatment of malignant gliomas. 1 UI - 87065556 AU - Kapp JP ; Sanford RA TI - Neurological deficit after carotid infusion of cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for malignant glioma: an analysis of risk factors. AB - The records of 24 patients with malignant gliomas treated with carotid infusion of cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are reviewed for risk factors that might suggest the development of a permanent neurological deficit after infusion. Permanent neurological deficits were seen with doses of cisplatin as low as 69 mg/m2, although doses as high as 100 mg/m2 were tolerated by other patients. All 3 patients who developed permanent neurological deficits received fixed doses of cisplatin of 150 mg and supplied only 2 major intracranial branches from the infused carotid artery. In none of these patients was a filter used in the infusion line. Other risk factors identified in 2 of the 3 patients were diffuse neoplasm involving the region of the internal capsule and the use of an infusion pump rather than a pulsatile bolus infusion technique. The development of a permanent neurological deficit appeared unrelated to the dose of BCNU within the range utilized, and preinfusion administration of corticosteroids did not prevent neurological deficit. These possible risk factors should be considered in the future development of protocols for arterial infusion therapy of malignant gliomas. MH - Brain Diseases/*CHEMICALLY INDUCED ; Brain Neoplasms/*DRUG THERAPY/RADIOGRAPHY ; Carmustine/*ADVERSE EFFECTS/THERAPEUTIC USE ; Carotid Artery, Internal ; Cisplatin/*ADVERSE EFFECTS/ THERAPEUTIC USE ; Glioma/*DRUG THERAPY/RADIOGRAPHY ; Human ; Infusions, Intra-Arterial ; Risk ; Tomography, X-Ray Computed SO - Neurosurgery 1986 Nov;19(5):779-83 2 UI - 87065518 AU - Neuwelt EA ; Howieson J ; Frenkel EP ; Specht HD ; Weigel R ; Buchan CG ; Hill SA TI - Therapeutic efficacy of multiagent chemotherapy with drug delivery enhancement by blood-brain barrier modification in glioblastoma. AB - Reversible osmotic blood-brain barrier (BBB) modification was used in 38 patients with glioblastoma to enhance the delivery of chemotherapeutic agents. The patients ranged in age from 14 to 70 years (mean, 43), and all had prior surgery and radiation; 5 had also received systemic chemotherapy. Karnofsky Performance Status (KPS) scores ranged from 60 to 100% (mean, 79) on admission to the treatment program. Barrier modification was achieved by intracarotid or intravertebral artery infusion of mannitol, and a chemotherapy regimen of methotrexate, cytoxan, and procarbazine was given in conjunction with barrier modification. The 38 glioblastoma patients were compared to two control groups of patients with glioblastoma; these encompassed 14 patients treated with surgery and radiation and 8 treated with surgery, radiation, and systemic chemotherapy. Survival analysis using the Cox Proportional Hazards Regression Model (corrected for age, sex, presence or absence of necrosis, and functional status) showed that patients receiving chemotherapy with BBB modification had a statistically significant (P = 0.0006) longer expected survival (17.5 months) than the control groups (12.8 and 11.4 months, respectively). Presently 16 patients of the barrier-enhanced treatment group are alive at 5 to 42 months from diagnosis (median, 20) with KPS scores ranging from 40 to 90% (median, 65). The neurological complications seen included a stroke-like syndrome in 3 patients (1 with decreased motor movement in the hand, 1 with marked hemiparesis, and 1 with hemiplegia), transient exacerbation of preexisting neurological deficits lasting 2 to 3 days, and a 15% incidence of seizures during or within 24 hours of the BBB modification. In 2 of the 38 patients, radiographic documentation of central nervous system tumor regression concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic BBB opening was seen. These studies indicate that chemotherapeutic drug delivery to tumors (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival. MH - Adult ; Aged ; Antineoplastic Agents, Combined/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Blood-Brain Barrier/*DRUG EFFECTS ; Brain Neoplasms/*DRUG THERAPY/PATHOLOGY/PHYSIOPATHOLOGY/ RADIOGRAPHY ; Female ; Glioma/*DRUG THERAPY/PATHOLOGY/ PHYSIOPATHOLOGY/RADIOGRAPHY ; Human ; Infusions, Intra-Arterial ; Male ; Mannitol/THERAPEUTIC USE ; Middle Age ; Prognosis ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. ; Tomography, X-Ray Computed SO - Neurosurgery 1986 Oct;19(4):573-82 3 UI - 87059974 AU - Vance RB ; Pittisapu J ; Kapp JP TI - Experiences with sodium thiosulfate after intracarotid infusion of cisplatin and BCNU for malignant gliomas. AB - The treatment of malignant gliomas with cisplatin has been shown to be of benefit. In order to reduce the side effects of the drug, we employed the use of sodium thiosulfate in ten patients one hour after cisplatin infusion and continued for 6 h. Side effects from this population of patients were compared with those side effects experienced with 13 patients not receiving thiosulfate. No real difference in number or severity of side effects from cisplatin was observed between the two groups although nephrotoxicity appeared to be reduced in the patients who received thiosulfate. MH - Adult ; Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Brain Neoplasms/*DRUG THERAPY ; Carmustine/ADMINISTRATION & DOSAGE ; Cisplatin/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Creatinine/BLOOD ; Female ; Glioma/*DRUG THERAPY ; Human ; Infusions, Intra-Arterial ; Male ; Middle Age ; Thiosulfates/ *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS SO - J Neurooncol 1986;4(2):151-4 4 UI - 87046243 AU - Millay RH ; Klein ML ; Shults WT ; Dahlborg SA ; Neuwelt EA TI - Maculopathy associated with combination chemotherapy and osmotic opening of the blood-brain barrier. AB - Eleven patients with intracranial malignant neoplasms underwent hyperosmotic opening of the blood-brain barrier by rapid mannitol infusion via the internal carotid or vertebral artery. Cyclophosphamide was administered intravenously preceding the mannitol infusion and methotrexate was infused after the mannitol via the same artery. Both the mannitol and methotrexate delivered via the carotid artery have direct access to the ipsilateral choroidal and retinal circulations. In these patients, retinal pigment epithelial changes eventually developed ipsilateral to the carotid infusions. The changes probably represent the toxicity of intraarterial methotrexate possibly potentiated by mannitol-induced opening of the blood-retinal barrier. Functional visual loss was minimal and was not a limiting factor with this therapeutic modality. MH - Adolescence ; Adult ; Blood-Brain Barrier/DRUG EFFECTS ; Brain Neoplasms/DRUG THERAPY ; Glioma/DRUG THERAPY ; Human ; *Macula Lutea/PATHOLOGY ; Mannitol/*ADVERSE EFFECTS/THERAPEUTIC USE ; Methotrexate/*ADVERSE EFFECTS/THERAPEUTIC USE ; Middle Age ; Osmosis ; Retinal Diseases/*CHEMICALLY INDUCED/PATHOLOGY ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Am J Ophthalmol 1986 Nov 15;102(5):626-32 5 UI - 87035818 AU - Cohen AR ; Pietronigro DD ; Cravioto H ; Flamm ES TI - Effect of difluoromethylornithine on the antiglioma therapeutic efficacy of intra-arterial BCNU. AB - In an attempt to improve glioma management, an animal model was developed to evaluate the therapeutic efficacy of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Furthermore, the model was used to study the antitumor activity of D,L-alpha-difluoromethylornithine (DFMO), a polyamine-biosynthesis inhibitor, used both as a single agent and in combination with intra-arterial BCNU. An N-methylnitrosourea-induced gliosarcoma (T9) was transplanted stereotaxically into the right caudate nucleus of male Fischer 344 rats. Animals receiving a single low-dose (5 mg/kg) intracarotid injection of BCNU 9 days following tumor implantation had a 57% increase in life span compared with untreated control rats (p less than 0.001). Intracarotid drug delivery was more effective than systemic (intraperitoneal) administration of the same dose of BCNU. When given as a single agent, DFMO demonstrated dose-dependent effectiveness. As part of a combined regimen, DFMO enhanced the antitumor therapeutic activity of both systemic (intraperitoneal) and intra-arterial BCNU. Survival times of animals receiving combined DFMO and intra-arterial BCNU were almost double those of untreated controls, and were significantly better than survival times of animals receiving combined DFMO and intraperitoneal BCNU. These findings suggest methods to optimize current clinical chemotherapy for glioma. MH - Alpha-Difluoromethylornithine/*THERAPEUTIC USE ; Animal ; Antineoplastic Agents, Combined ; Brain Neoplasms/*DRUG THERAPY/ MORTALITY ; Carmustine/*THERAPEUTIC USE ; Comparative Study ; Glioma/*DRUG THERAPY/MORTALITY ; Injections, Intra-Arterial ; Male ; Neoplasm Transplantation ; Rats ; Rats, Inbred F344 ; Time Factors SO - J Neurosurg 1986 Nov;65(5):671-8 6 UI - 87035716 AU - Schlenska GK TI - Absence of both internal carotid arteries. AB - A 63-year-old man developed a slight left hemiparesis. CT scan showed an intracerebral tumour, which was later identified as glioblastoma multiforme. Angiographic examination revealed the absence of both internal carotid arteries. Blood supply of anterior and middle cerebral arteries was provided by communication between a tortuous megadolichobasilar artery and the circle of Willis through enlarged posterior communicating arteries. The case is reported with reference to clinical symptoms as well as angiographic and anatomical findings of 17 comparable cases mentioned in literature. MH - Basal Ganglia ; Brain Neoplasms/COMPLICATIONS ; Carotid Arteries/ *ABNORMALITIES ; Carotid Artery, Internal ; Case Report ; Cerebral Angiography ; Cerebral Ventricle Neoplasms/COMPLICATIONS ; Glioblastoma Multiforme/COMPLICATIONS ; Human ; Male ; Middle Age ; Tomography, X-Ray Computed SO - J Neurol 1986 Oct;233(5):263-6 7 UI - 87035189 AU - Leahy NM TI - Intraarterial cisplatin infusion: nursing implications. AB - Patients diagnosed with malignant intracranial tumors have limited chemotherapeutic options. Recent studies have shown that intraarterial infusions of antineoplastic agents to regionally confined malignancies may be of great benefit. Clinical trials of intraarterial infusions of the drug cisplatin are investigating its efficacy in treating intracerebral gliomas. This paper presents the rationale for such treatment and emphasizes nursing responsibilities relative to the treatment protocols. MH - Blood-Brain Barrier ; Brain Neoplasms/*DRUG THERAPY/ PHYSIOPATHOLOGY ; Cell Cycle ; Cisplatin/*ADMINISTRATION & DOSAGE/ METABOLISM ; Glioma/*DRUG THERAPY/PHYSIOPATHOLOGY ; Human ; Infusions, Intra-Arterial/*NURSING ; *Nursing Assessment ; *Nursing Diagnosis ; Patient Discharge SO - J Neurosci Nurs 1986 Oct;18(5):296-301 8 UI - 87015299 AU - Foo SH ; Choi IS ; Berenstein A ; Wise A ; Ransohoff J ; Koslow M ; George A ; Lin J ; Feigin I ; Budzilovich G ; et al TI - Supraophthalmic intracarotid infusion of BCNU for malignant glioma. AB - We treated five patients with 11 supraophthalmic infusions of BCNU at 200 mg/m2 every 2 months. All three patients with residual tumors showed marked CT response after one infusion. Two patients with bilateral tumors had no response on the contralateral side. All four evaluable cases showed evidence of BCNU neurotoxicity. CT findings superficially resembled tumor recurrence, but white matter changes, nonspecific gyral enhancement, and delayed calcification were more indicative of neurotoxicity. There were no procedure-related complications. One autopsy suggested that direct parenchymal damage might be responsible for delayed neurotoxicity. Supraophthalmic BCNU infusion, at this dosage, is too toxic for cerebral tissue. MH - Adult ; Brain Neoplasms/*DRUG THERAPY ; Carmustine/ *ADMINISTRATION & DOSAGE ; Female ; Glioma/*DRUG THERAPY ; Human ; Infusions, Intravenous ; Male ; Middle Age ; Support, U.S. Gov't, P.H.S. SO - Neurology 1986 Nov;36(11):1437-44 9 UI - 86231193 AU - De Chiara A ; Benvenuti D ; Maiuri F ; Giamundo A ; Lavano A TI - Association of internal carotid aneurysm and temporal glioblastoma. AB - A 52-year-old woman had a right temporal glioblastoma six months after an operation for a right internal carotid aneurysm. In the literature there are no reports of gliomas arising in the region of a preceding craniotomy for an aneurysm. The rare association of brain tumours with arterial aneurysms and the pathogenetic theories are discussed. The authors suppose that in their case there is a relationship between the vascular changes due to the aneurysm and the operation and the growth of the malignant glioma. MH - Brain Neoplasms/*ETIOLOGY/SURGERY ; Carotid Artery Diseases/ *SURGERY ; Carotid Artery, Internal/SURGERY ; Case Report ; Cerebral Aneurysm/*SURGERY ; Female ; Glioma/*ETIOLOGY/SURGERY ; Human ; Middle Age ; Postoperative Complications/*ETIOLOGY/ SURGERY ; *Temporal Lobe/SURGERY ; Tomography, X-Ray Computed SO - Neurochirurgia (Stuttg) 1986 Mar;29(2):58-60 10 UI - 86226664 AU - Tyler JL ; Yamamoto YL ; Diksic M ; Th:eron J ; Villemure JG ; Worthington C ; Evans AC ; Feindel W TI - Pharmacokinetics of superselective intra-arterial and intravenous [11C]BCNU evaluated by PET. AB - The pharmacokinetics of i.v. and superselective intra-arterial carbon-11 1,3-bis-(2-chloroethyl)-1-nitrosourea ([11C]BCNU) were directly compared for the first time in ten patients with recurrent gliomas using positron emission tomography (PET). Intra-arterial administration of [11C]BCNU achieved concentrations of the drug in the tumor that averaged 50 times higher than with a comparable i.v. dose. These preliminary results suggest that the degree of early metabolic trapping of BCNU in tumor correlates with the clinical response to this chemotherapy. MH - Adult ; Aged ; Brain Neoplasms/BLOOD/*DRUG THERAPY/RADIONUCLIDE IMAGING ; Carbon Radioisotopes/DIAGNOSTIC USE ; Carmustine/ ADMINISTRATION & DOSAGE/*BLOOD ; Drug Evaluation ; Female ; Glioma/BLOOD/*DRUG THERAPY/RADIONUCLIDE IMAGING ; Half-Life ; Human ; Injections, Intra-Arterial ; Injections, Intravenous ; Kinetics ; Male ; Middle Age ; Support, Non-U.S. Gov't ; Tomography, Emission Computed SO - J Nucl Med 1986 Jun;27(6):775-80 11 UI - 86204065 AU - Th:eron J ; Villemure JG ; Worthington C ; Tyler JL TI - Superselective intracerebral chemotherapy of malignant tumours with BCNU. Neuroradiological considerations. AB - Early experience shows that: Superselective intra-arterial catheterization above the ophthalmic artery minimizes the orbital complications. Catheterization in a distal branch may lead to the non-infusion of a part of the tumor territory. A much higher concentration of the drug is achieved by superselective intra-arterial infusion than by intravenous injection. Longer infusions seem more efficacious than bolus injection. Early trapping of the drug appears to be essential for therapeutic efficacy. MH - Blood-Brain Barrier ; Brain/PATHOLOGY ; Brain Neoplasms/*DRUG THERAPY/RADIOGRAPHY ; Carmustine/*ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/THERAPEUTIC USE ; Carotid Artery, Internal ; Catheterization/ADVERSE EFFECTS/METHODS ; Cerebral Angiography ; Glioma/*DRUG THERAPY/RADIOGRAPHY ; Human ; Injections, Intra-Arterial ; Necrosis ; Tomography, X-Ray Computed ; Vision Disorders/CHEMICALLY INDUCED SO - Neuroradiology 1986;28(2):118-25 12 UI - 86178434 AU - Doppman JL ; Dedrick RL ; Shook DR ; Lutz RJ ; Goldstein SR ; Blacklock JB ; Boretos JW ; Paul RH ; Austin HA 3d ; Bowman RL ; et al TI - Glioblastoma: catheter techniques for isolated chemotherapy perfusion. AB - Techniques have been developed for isolated perfusion of chemotherapeutic agents in patients with glioblastoma. Three catheters that facilitate crossing the carotid siphon have been developed; two are based on an everting or toposcopic principle, and one uses microjets for deflectability and improved mixing. Blood from the ipsilateral jugular vein is aspirated at high volumes (300 ml/min) for extracorporeal circulation through an adsorption column (for recovery of carmustine) or dialysers (for recovery of cisplatin). Preliminary experience in 10 patients suggests that high doses of chemotherapeutic agent can be administered using these catheters, with reduced retinal and systemic toxicity. MH - Brain Neoplasms/*DRUG THERAPY/RADIOGRAPHY ; Carotid Artery, Internal ; Catheterization/INSTRUMENTATION/*METHODS ; Glioma/ *DRUG THERAPY/RADIOGRAPHY ; Human ; Infusions, Intra-Arterial/ INSTRUMENTATION/*METHODS ; Jugular Veins ; Perfusion, Regional/ INSTRUMENTATION/*METHODS SO - Radiology 1986 May;159(2):477-83 13 UI - 86175324 AU - Heppner F TI - The glioblastoma multiforme: a lifelong challenge to the neurosurgeon. AB - During a period of 34 years 1316 gliomas of the brain have been treated, among them 508 glioblastomas (= 39%). In addition to the operative removal and postoperative X-ray therapy of glioblastomas various attempts have been undertaken to prevent recurrences: Intracerebral application of Cobalt60 (6 patients); locally applied antimitotic agents (76 patients); bacterial liquefaction induced by intracarotid administration of Clostridium butyricum M 55 spores ("Oncolysis:, 67 patients); circumscribed heating of the extirpation cavity with metal and high-frequency electromagnetic field (85 patients); vaporization of the tumour bed with the defocussed CO2- or Neodymium-YAG-Laser beam (177 patients). Permanent cure has been attained only in single cases so that the problem does not yet seem to be definitely solved by any of these methods. However, bacterial oncolysis in combination with the periodic postoperative generation of heat locally in the excision cavity of the tumour, might justify cautious optimism about future developments. MH - Brachytherapy ; Brain Neoplasms/*SURGERY ; Clostridium ; Cobalt Radioisotopes/THERAPEUTIC USE ; Combined Modality Therapy ; Glioblastoma Multiforme/*SURGERY ; Human ; Hyperthermia, Induced ; Lasers/THERAPEUTIC USE ; Neoplasm Recurrence, Local/*SURGERY ; Prognosis SO - Neurochirurgia (Stuttg) 1986 Jan;29(1):9-14 14 UI - 86170670 AU - Klein DS ; Klein PW ; Mahaley MS Jr TI - Nalbuphine and droperidol in combination for sedation and prevention of nausea and vomiting during intra-carotid BCNU infusion. AB - A therapeutic regimen is described for sedative, analgesic, and anti-emetic effect in patients receiving intra-arterial carmustine (BCNU) for malignant gliomas. This regimen consists of nalbuphine, 30 mg, i.v., and droperidol, 2.5 mg, i.v., given immediately prior to intra-carotid BCNU infusion. Droperidol, 2.5 mg, i.v., is then administered on four hour intervals for sixteen hours post-procedure. This combination provided excellent effect in nine patients treated for twelve intra-carotid infusions. None of the nine patients experienced vomiting, one experienced mild nausea several hours post-infusion, and non complained of severe pain or discomfort. Thirteen additional patients received diazepam, 10 mg, P.O., prior to the intra-carotid BCNU infusion, with fentanyl, 100 mcg, i.v., and prochlorperazine, 10 mg, i.m. at the onset of infusion. All thirteen patients suffered from severe nausea, vomiting, and orbital pain. The nalbuphine/droperidol combination is thought to provide a superior alternative to the traditional narcotic/pheonothiazine/benzodiazepine combination for carotid BCNU infusion. This combination has theoretical advantages for the patient with intracranial mass lesions by providing analgesia and sedation with minimal potential for respiratory depression and carbon dioxide retention. MH - Adult ; Aged ; Brain Neoplasms/DRUG THERAPY ; Carmustine/ ADMINISTRATION & DOSAGE/*ADVERSE EFFECTS ; Carotid Arteries ; Diazepam/THERAPEUTIC USE ; Droperidol/*THERAPEUTIC USE ; Drug Therapy, Combination ; Fentanyl/THERAPEUTIC USE ; Glioma/DRUG THERAPY ; Human ; Injections, Intra-Arterial ; Middle Age ; Morphinans/*THERAPEUTIC USE ; Nalbuphine/*THERAPEUTIC USE ; Nausea/*PREVENTION & CONTROL ; Prochlorperazine/THERAPEUTIC USE ; Vomiting/*PREVENTION & CONTROL SO - J Neurooncol 1986;3(4):323-5 15 UI - 86170668 AU - Mahaley MS Jr ; Whaley RA ; Blue M ; Bertsch L TI - Central neurotoxicity following intracarotid BCNU chemotherapy for malignant gliomas. AB - Central neurotoxicity is reported in 5 of 16 patients with recently diagnosed anaplastic gliomas, who received intra-arterial BCNU (200 mg/M2/course) and also 2 in a series of 26 patients with recurrent gliomas similarly treated. Neurotoxicity was usually delayed, commencing several weeks following the second or third course. CT scans during central neurotoxicity represented 1 or more of 3 patterns: no change; increased low density area(s); and/or ipsilateral gyral enhancement and punctate calcification in the middle cerebral artery territory. In one clinicopathological correlation, coagulative necrosis of the white matter was observed, identical histologically to those changes recognized as delayed vascular events following radiotherapy. Cautious exploration of the various clinical factors that may contribute to this toxicity seems appropriate, as exploration of the potential benefits of regional chemotherapeutic infusions is undertaken. MH - Brain Neoplasms/*DRUG THERAPY/PATHOLOGY ; Carmustine/ *ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Glioma/*DRUG THERAPY/ PATHOLOGY ; Hemiplegia/CHEMICALLY INDUCED ; Human ; Injections, Intra-Arterial ; Support, U.S. Gov't, P.H.S. ; Time Factors ; Tomography, X-Ray Computed SO - J Neurooncol 1986;3(4):297-314 16 UI - 86170667 AU - Mughal TI ; Glode LM ; Braun TJ ; Klingensmith W ; Geier JM ; Kindt GW TI - Phase I clinical trial of intracarotid bis-chloroethylnitrosourea (BCNU) and 2' dioxy-5-fluorouridine (FUDR) in malignant astrocytomas. AB - Systemic chemotherapy has been of limited benefit in the treatment of intracranial neoplasms, due, in part, to the inability to deliver effective drug doses to the neoplasm without systemic toxicity. We have completed a clinical trial of intracarotid BCNU and FUDR using an implantable pump in patients with unilateral malignant astrocytomas (Grade III and IV) in the hope of obtaining better tumor control with less systemic toxicity. Six patients had in-dwelling catheters placed in the internal carotid artery attached to a percutaneous refillable pump (Infusaid 400). The treatment program consisted of bolus BCNU 400 mg every 6 weeks and FUDR by continuous infusion at dosages ranging from 0.5 mg/24 h to 2.5 mg/24 h. The maximum tolerable dose of FUDR was 1 mg/24 h with ipsilateral mucositis and conjunctivitis being dose limiting factors. Flow studies demonstrated significant perfusion of the ipsilateral eye and surrounding face secondary to ophthalmic artery collaterals. No patient had systemic toxicity and the lowest WBC encountered was 2 400 with normal differential and platelets. MH - Aged ; Antineoplastic Agents, Combined/*THERAPEUTIC USE ; Astrocytoma/*DRUG THERAPY ; Brain Neoplasms/*DRUG THERAPY ; Carmustine/*ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Carotid Arteries ; Drug Evaluation ; Female ; Fluorodeoxyuridine/ *ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Human ; Injections, Intra-Arterial ; Male ; Middle Age ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - J Neurooncol 1986;3(4):291-6 17 UI - 86170666 AU - Vance RB ; Kapp JP TI - Supraophthalmic carotid infusion with low dose cisplatin and BCNU for malignant glioma. AB - Arterial infusion of select chemotherapeutic agents has been shown to deliver increased drug concentration to brain tumors with reduced systemic toxicity. In this study, nine patients with histologically confirmed malignant glioma received cisplatin 110 mg and BCNU 300 mg fixed dose. All patients had received standard doses of cranial radiation after their initial surgical procedures. In three patients, intraoperative modification of the cerebral circulation was accomplished prior to the actual infusion because the vascular supply of the tumor arose from major arteries other than a single internal carotid artery. Supraophthalmic catheterization technique was employed. No neurological deficits occurred post infusion. The radiographic response rate was 25%. No responses were seen in patients who received less than 69 mg/M2 cisplatin this combination. The longest survival is 11+ months in a patient with anaplastic astrocytoma. Our first thirteen patients received cisplatin 150-200 mg and BCNU 300 mg for each infusion with a response rate of 83% in evaluable patients. Since modest reduction in cisplatin dose dramatically reduced the response rate, future studies should be directed at fine tuning the dose of this drug, or at neutralizing recirculating drug after its high dose first pass through the arterial circulation. MH - Brain Neoplasms/*DRUG THERAPY ; Carmustine/*ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Carotid Arteries ; Cisplatin/ *ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Dose-Response Relationship, Drug ; Glioma/*DRUG THERAPY ; Human ; Injections, Intra-Arterial ; Tomography, X-Ray Computed SO - J Neurooncol 1986;3(4):287-90 18 UI - 86161454 AU - Greenberg HS ; Ensminger WD ; Layton PB ; Gebarski S ; Meyer M ; Chaffee B ; Bender JF ; Grillo-Lopez AJ TI - Phase I-II evaluation of intra-arterial diaziquone for recurrent malignant astrocytomas. AB - Diaziquone (AZQ) is a lypophilic alkylating agent that crosses the blood-brain barrier and has shown broad activity in animal tumor models. Five of 12 patients with malignant astrocytoma treated with iv AZQ had clinical and/or radiographic improvement (Schold, Neurology 34:615, 1984). Intra-arterial administration of AZQ to patients with brain tumors should produce higher peak levels of drug in the tumor and should reduce systemic toxicity. Twenty-one patients with astrocytoma (grade II, four; grade III, 11; and grade IV, six), in all of whom irradiation and intra-arterial carmustine chemotherapy failed, received intra-arterial AZQ as a single dose every 28 days. Two of 20 evaluable patients experienced partial responses of 5 and 8+ months, respectively. Four patients had disease stabilization of 3, 4, 5, and 8 months' duration, respectively, and one of these patients had tumor shrinkage (partial response) after seven courses of AZQ. The initial dose in the first three patients was 10 mg/m2, and doses in subsequent groups of three patients were begun at increases of 5 mg/m2. The within-group dose escalation was 5 mg/m2 per course if there was no hematologic toxicity. Dose-limiting toxicity was myelosuppression, which occurred at doses greater than 15 mg/m2. The maximum tolerated dose was 25 mg/m2. Intra-arterial AZQ appears to be of marginal effectiveness in patients refractory to carmustine and offers no advantage over iv AZQ in efficacy or toxicity. MH - Adult ; Aged ; Antineoplastic Agents/ADVERSE EFFECTS/METABOLISM/ *THERAPEUTIC USE ; Astrocytoma/*DRUG THERAPY ; Aziridines/ADVERSE EFFECTS/METABOLISM/*THERAPEUTIC USE ; Azirines/*THERAPEUTIC USE ; Bone Marrow/DRUG EFFECTS ; Brain Neoplasms/*DRUG THERAPY ; Carmustine/THERAPEUTIC USE ; Drug Evaluation ; Eye/DRUG EFFECTS ; Female ; Glioblastoma Multiforme/*DRUG THERAPY ; Human ; Infusions, Intra-Arterial ; Male ; Middle Age ; Neoplasm Recurrence, Local/*DRUG THERAPY ; Support, Non-U.S. Gov't SO - Cancer Treat Rep 1986 Mar;70(3):353-7 19 UI - 86142142 AU - Resio MJ ; DeVroom HL TI - Spiromustine and intracarotid artery cisplatin in the treatment of glioblastoma multiforme. AB - Glioblastoma multiforme is a highly malignant and rapid-growing primary brain tumor. It constitutes one-fourth of all intracranial tumors and about half of all gliomas. Survival rate following conventional treatment is only 12 to 18 months. At the National Institutes of Health, two promising therapies are currently undergoing clinical trials. Spirohydantoin mustard (spiromustine) is a combination of a nitrogen mustard and a derivative of phenytoin, an anticonvulsant drug that rapidly penetrates the blood-brain barrier and localizes in brain tumors. Intracarotid administration of cis-diamminedichloroplatinum (cisplatin) increases drug delivery to the tumor and, through hemodialysis, systemic exposure is reduced. Nursing management of patients receiving these two agents requires precise planning and implementation of an individualized plan of care to ensure a successful chemotherapeutic regimen. MH - Brain Neoplasms/*DRUG THERAPY/NURSING/PHYSIOPATHOLOGY/THERAPY ; Carotid Arteries ; Cisplatin/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE ; Combined Modality Therapy ; Drug Evaluation ; Glioblastoma Multiforme/*DRUG THERAPY/NURSING/ PHYSIOPATHOLOGY/THERAPY ; Human ; Hydantoins/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC USE ; Infusions, Intra-Arterial ; National Institutes of Health (U.S.) ; Nitrogen Mustard Compounds/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/ *THERAPEUTIC USE ; Oncologic Nursing ; United States SO - J Neurosci Nurs 1986 Feb;18(1):13-22 20 UI - 86133091 AU - Kleinschmidt-DeMasters BK TI - Intracarotid BCNU leukoencephalopathy. AB - Intracarotid 1,3-bis(2-chloroethyl)-1-nitrosurea (BCNU) is now a frequently used chemotherapeutic agent for high-grade glial neoplasms. The toxicity from such therapy has not been well-documented. A 50-year-old man with a left frontoparietal grade 4 astrocytoma received three injections of intracarotid BCNU, 400 mg each, over a 2-month period. No radiation or other chemotherapy was ever given. He tolerated the BCNU injections well, with some reduction of tumor bulk, until the third dose. After his last injection, his condition gradually deteriorated; he became obtunded, and died 5 weeks later. At autopsy, the brain showed extensive cavitation and coagulative necrosis, fibrinoid vascular necrosis, edema, swollen axons, and bizarre cellular morphologic features confined to the BCNU perfusion territory. Grade 4 astrocytoma remained in the right hemisphere and in the left occipital lobe, sites outside the area of BCNU perfusion. Intracarotid BCNU can result in a severe leukoencephalopathy similar to that seen with methotrexate or delayed radionecrosis. MH - Astrocytoma/DRUG THERAPY ; Autopsy ; Brain/DRUG EFFECTS/PATHOLOGY ; Brain Neoplasms/DRUG THERAPY ; Carmustine/*ADVERSE EFFECTS ; Carotid Artery, Internal ; Case Report ; Human ; Infusions, Intra-Arterial ; Leukoencephalopathy, Progressive Multifocal/ *CHEMICALLY INDUCED/PATHOLOGY ; Male ; Middle Age ; Necrosis/ PATHOLOGY ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cancer 1986 Apr 1;57(7):1276-80 21 UI - 86129136 AU - Hiesiger EM ; Voorhies RM ; Basler GA ; Lipschutz LE ; Posner JB ; Shapiro WR TI - Opening the blood-brain and blood-tumor barriers in experimental rat brain tumors: the effect of intracarotid hyperosmolar mannitol on capillary permeability and blood flow. AB - Using quantitative autoradiography, we investigated the effect of intracarotid infusions of hyperosmolar mannitol solutions on capillary permeability and blood flow. Capillary permeability, expressed in terms of a blood-to-tissue transfer constant (K), was determined in two rat brain tumor models by measuring the entry of 14C-alpha aminoisobutyric acid into brain tumor, into brain tissue adjacent to tumor, and into cortex. Cerebral blood flow was determined by measuring the uptake of 14C-iodoantipyrine in one rat brain tumor model. Blood flow was examined in the same regions as K, as well as in the corpus callosum. Before mannitol administration, K values in both Walker 256 (W256) carcinosarcoma and C6 gliomas were much higher than those in cortex. C6 gliomas were about three times more permeable than were W256 tumors. There was a direct correlation between tumor size and increased capillary permeability. Mannitol at a concentration of 1.37 M did not increase the K values for either tumor or adjacent tissue. At 1.6 M, mannitol increased the K values for both tumors (1.7-fold in C6 glioma and 13-fold in W256) as well as for adjacent tissue. At both concentrations, mannitol markedly increased cortical K values in all groups: by 48- to 72-fold at 1.37 M and by 90- to 105-fold at 1.6 M. The net effect of the mannitol was to reverse the tumor-to-cortex permeability relationship. Cortical blood flow increased modestly after intracarotid mannitol administration on both sides of the brain. These data provide little justification for using intracarotid mannitol during chemotherapy of human brain tumors. MH - Animal ; Blood-Brain Barrier/*DRUG EFFECTS ; Brain Neoplasms/ *BLOOD SUPPLY/SECONDARY ; Capillary Permeability/*DRUG EFFECTS ; Carcinosarcoma/*BLOOD SUPPLY/SECONDARY ; Carotid Arteries ; Cerebral Cortex/BLOOD SUPPLY ; Cerebrovascular Circulation/*DRUG EFFECTS ; Glioma/*BLOOD SUPPLY ; Injections, Intra-Arterial ; Male ; Mannitol/*PHARMACODYNAMICS ; Osmolar Concentration ; Rats ; Rats, Inbred Strains ; Regional Blood Flow/DRUG EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Ann Neurol 1986 Jan;19(1):50-9 22 UI - 86097309 AU - Kapp JP TI - Vascular diversion in chemotherapy of brain tumors. AB - Of the patients with malignant gliomas treated by arterial infusion of chemotherapeutic agents at one institution, tumor extension beyond the territory supplied by a single internal carotid artery was documented at operation or by computed tomography or angiography in 55%. In 47% of the patients, a surgical procedure was performed to modify the cerebral circulation so that the entire lesion could be treated by infusing a single internal carotid artery. This report examines the anatomical and radiological background for these procedures, and the surgical options, techniques, and complications in this series of patients. MH - Antineoplastic Agents/ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Carotid Arteries ; Cerebellar Neoplasms/*DRUG THERAPY/RADIOGRAPHY ; Cerebral Angiography ; *Cerebral Revascularization ; Circle of Willis/SURGERY ; Glioma/*DRUG THERAPY/RADIOGRAPHY ; Human ; Infusions, Intra-Arterial ; Tomography, X-Ray Computed SO - Surg Neurol 1986 Jan;25(1):33-8