Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.
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PMID:Combined intraarterial and systemic chemotherapy for intracerebral tumors. 244 73

Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.
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PMID:Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine. 254 93

Fifteen patients, 12 with glioblastoma multiforme and 3 with anaplastic astrocytoma, were treated with "eight-drugs-in-one-day" chemotherapy [methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 (maximum of 2 mg/cycle), CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3,000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2]. All patients had prior brain irradiation but none had previous chemotherapy. The population included 10 patients with progressive disease after irradiation and 5 who presented within 2 months of completing radiation. Patients received an average of 5 monthly cycles of chemotherapy. Three patients achieved a complete and 2 a partial response (CR + PRrate was 33%). The median survival time was 46 weeks. Myelosuppression was the dose-limiting toxicity. Leucocyte counts between 2.0-4.5 x 10(3)/mm3 were observed in 40% of patients, between 1.0- less than 2.0 x 10(3)/mm3 in 33%, and less than 1.0 x 10(3)/mm3 in 7%. Platelet counts between 50-130 x 10(3)/mm3 were observed in 27% of patients, and less than 50 x 10(3)/mm3 in 33%. Six patients suffered infections, 4 had reversible renal toxicity, 2 developed paresthesias, and one a debilitating myopathy related to treatment with dexamethasone. Ototoxicity was seen in 3 patients. Two patients developed pulmonary emboli. Nine patients had nausea and vomiting, in one case associated with Candida esophagitis. One long-term survivor developed necrosis of the corpus callosum and dementia. Four patients discontinued treatment after an average of 3.5 cycles because of toxicity. Although extremely toxic, this regimen has modest activity in previously irradiated adult patients with malignant glioma.
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PMID:Eight-drugs-in-one-day chemotherapy in postirradiated adult patients with malignant gliomas. 258 61

Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.
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PMID:"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas. 272 May 98

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas.
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PMID:Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas. 304 41

Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.
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PMID:Combination intraventricular chemotherapy for meningeal neoplasia. 307 22

Carboplatin is one of a series of cisplatin analogs now undergoing clinical investigation. Phase I and II trials in adults demonstrate activity in a number of human cancers and less toxicity than might be expected with the parent compound. This phase I trial was undertaken to establish the maximum tolerated dose and the recommended phase II dose in children treated by a 1-hour iv infusion every 4 weeks. Twenty-nine patients with recurrent or progressive tumor were entered in this study at the Children's Hospital of Los Angeles and Children's Memorial Hospital in Chicago between April 12, 1983, and November 27, 1984. Beginning with a dose of 350 mg/m2 (about 80% of the adult phase II dose), we escalated the dose in groups of patients to 670 mg/m2; dose-limiting myelosuppression was encountered at this dose. Fifty-seven infusions are at least partially evaluable for toxicity. Asymptomatic hypomagnesemia, hypocalcemia, and ototoxicity were observed infrequently, and nausea and vomiting were mild. One patient with a mixed glioma of the posterior fossa achieved a good partial response lasting 9 months. Stable disease for greater than or equal to 6 months was observed in three patients: one each with ependymoma, brain stem glioma, and spinal cord astrocytoma. The recommended pediatric phase II dose is 560 mg/m2 given as a 1-hour iv infusion every 4 weeks.
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PMID:Pediatric phase I trial of carboplatin: a Childrens Cancer Study Group report. 331 95

In order to analyze the efficacy of combination therapy with Hu-IFN-beta, ACNU and radiation (IAR), nine patients with malignant glioma were treated as a control study. They received 100 X 10(4) IU Hu-IFN-beta daily for seven days intravenously or intratumorally, 3 mg/kg ACNU on day 2 and 5,000-6,000 rads of radiation from day 3. Four out of nine patients showed complete response and one partial response with this IAR therapy. Case 1 was a 64-year-old man who had glioblastoma in the left frontal lobe. Postoperative residual tumors disappeared completely with this therapy. Case 3 was a 8-year-old girl who had an enhanced high-density lesion in the medulla oblongata and pons. After IAR therapy, the high-density lesion was completely vanished and her clinical manifestations of multiple cranial nerve palsy and pyramidal sign were improved remarkably. The major side effects of IAR therapy were mild or moderate myelosuppression, and some patients also showed hepatic dysfunction, mild fever and gastrointestinal toxicities. However, all these side effects were mild and transient and soon recovered to normal levels. These results suggest that IAR therapy is effective and will prolong the survival time of patients with malignant glioma.
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PMID:[Combination therapy with IFN-beta, ACNU and radiation (IAR) in malignant brain tumors]. 345 40

Eleven patients with recurrent malignant glioma were treated with single high doses of BCNU ranging from 600 to 1400 mg/sq m. To prevent the characteristic late myelosuppression observed after conventional doses of BCNU, autologous bone marrow harvested just before drug treatment was infused 24 to 36 hours after therapy. Higher doses of BCNU causes earlier and more profound myelosuppression; one patient died on pancytopenia, breakdown of the gut epithelium, and Clostridium septicemia 10 days after receiving 1400 mg/sq m of BCNU. All patients experienced transient emesis; four developed transient elevation of hepatic enzymes, two reversible interstitial pulmonary infiltrates, and two who received 1400 mg/sq m BCNU suffered irreversible cortical damage. Eight patients receiving 600 to 1200 mg/sq m demonstrated reconstitution of polymorphonuclear leukocytes an platelets within at least 30 days after treatment. With a follow-up time of up to 19 months, four patients improved, three stabilized, and three deteriorated and died. The median survival time was 7 months. Computerized tomography performed on patients receiving constant corticosteroids showed diminished contrast enhancement and mass effect in eight patients. High-dose BCNU at doses up to 1200 mg/sq m with marrow rescue is a feasible approach to the treatment of patients with glioblastoma.
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PMID:High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. 625

Spiromustine is a new alkylating agent, of interest since it was rationally designed as a lipophilic compound capable of penetrating the CNS. This lipophilicity may also enhance alkylating activity against tumors other than brain tumors. Preclinical screening has shown activity against a variety of tumors, including an intracranially implanted ependymoblastoma. Alkylating activity has been demonstrated in an intracerebral glioma in the rat. Spiromustine is a cell cycle non-specific agent. Animal pharmacology studies have shown a biphasic plasma decay curve, with hepatic metabolism and excretion, an enterohepatic circulation of metabolites, and approximately 50% renal excretion of unchanged drug. Toxicology studies in mice, rats and dogs showed that dose-related myelosuppression, and neurotoxicity predominated; other organ toxicities were mild. Spiromustine is currently entering Phase I clinical trials on a variety of schedules.
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PMID:Spiromustine: a new agent entering clinical trials. 638 79


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