Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side-effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2-year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy.
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PMID:Phase II study of tauromustine in malignant glioma. 141 89

This study was undertaken to determine the maximum tolerated dose of aziridinylbenzoquinone (AZQ) given as a 24-hour intravenous infusion every 21-28 days. Thirty-four patients with recurrent or progressive gliomas received AZQ at a dose of 25, 30, 35, 40, or 45 mg/m2. At a dose of 45 mg/m2, leukopenia and thrombocytopenia of grade 3 or greater was observed in 42% and 25% of patients respectively; no patient required transfusion or antibiotics for fever. For administration of AZQ at a 24-hour intravenous infusion, we recommend a starting dose of 40 mg/m2 for patients without previous exposure to cytotoxic agents, and 35 mg/m2 for patients treated with such agents. In 14 patients with glioblastoma, tumor regression was observed in 1 patient (14%) and stabilization of disease was demonstrated in 7 patients (50%). In 17 patients with anaplastic astrocytomas there were no responses, but 8 patients (47%) stabilized. Of two patients with an oligodendroglioma, one continues without progression at 34 weeks after initial response. One patient with malignant ependymoma stabilized and had not progressed at 39 weeks. The median time to tumor progression in patients who stabilized and responded was 18 weeks for those with glioblastoma multiforme and 16 weeks in those with anaplastic astrocytomas.
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PMID:A phase I/II study of 24 hour intravenous AZQ in recurrent primary brain tumors. 322 Dec 59

A phase II study of recombinant interferon alpha A (Ro 22-8181) for malignant brain tumors was jointly conducted at 21 medical institutes in order to evaluate its clinical effects and side effects. Treatment started with exclusive administration of Ro 22-8181 at 3 X 10(6) U/day, which was increased appropriately after confirmation of its safety, until an optimum dose permitting long-term administration was achieved for each patient. The dose thus determined was intramuscularly administered daily. Among those treated, 39 patients were available for evaluation. The percentage of partial responses according to the "Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor" by Koyama and Saito was 10.3% (4/39). Histologically, this was 7.1% (1/14) for glioblastoma and 14.3% (3/21) for malignant astrocytoma. Side effects included fever (57.3%), anorexia (34.1%), general fatigue (31.7%), leukopenia (52.4%) and thrombocytopenia (30.5%), and increased GOT and GPT (40.2%). In view of the success even in previously treated patients, and the side effects observed, Ro 22-8181 may be accepted as a useful addition to the treatment of malignant brain tumors.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in malignant brain tumors]. 388 62

Based on preliminary favorable results with the use of postoperative high-dose radiation therapy for malignant gliomas and encouraging experimental studies which indicated that fractionated does of BCNU given 16 hours before irradiation significantly enhanced the effect of radiation both in vitro and in vivo, the Eastern Cooperative Oncology Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of BCNU in a high-risk Phase I-II pilot study. The radiation therapy consisted of delivering 6000 rad to the whole brain plus a boost of 1000 rad to the tumor. BCNU was given i.v. 16 hours before the next radiation fraction with doses of 20 mg/M2 twice weekly for six weeks beginning on the second day of irradiation. Twelve patients were treated (5 with Grade III and 7 with Grade IV Astrocytomas). The median survival for the entire group was 80 weeks (30 weeks for Grade IV and 210 weeks for Grade III tumors). These results are not difficult from what was achieved by high-dose radiation alone. Subsequent experimental data seem to indicate that probably the smallest dose of BCNU that should be used in pulsed BCNU combined modality therapy is 80 mg/M2. In general, the treatment as offered in this study was well tolerated. There were no fatal or life-threatening hematologic toxicities and only one patient exhibited a transitory leukopenia of 1600.
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PMID:High-dose radiation therapy with low-dose (pulsed) BCNU in malignant gliomas: an Eastern Cooperative Oncology Group (ECOG) report. 628 58

Twenty-five adults who harbored malignant gliomas received 72 courses of intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 mg/m2) and 67 courses of systemic vincristine (1.0 mg/m2) and procarbazine (100 mg/m2) as induction therapy (BVP) followed by 106 courses of systemic 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU) (130 mg/m2), vincristine, and procarbazine as maintenance therapy (MVP). With a 6-week interval between each treatment, the median and range for the number of courses of BVP were 3 and 1 to 4 and those for MVP were 3 and 0 to 14, respectively. Fifteen patients (60%) responded to both BVP and MVP, and 10 (40%) did not. The overall median survival time was 12.7 months (range, 1.8 to 48.5+ months). Two of 3 patients who had recurrent gliomas responded and survived for 37+ to 45+ months. Seven of 10 who had nonirradiated glioblastomas responded and survived for 9 to 22 months. Four who had nonirradiated anaplastic astrocytomas all responded and survived for 38+ to 48.5+ months. Two who also received radiotherapy (1 glioblastoma and 1 primitive neuroectodermal tumor) benefited and survived for 16.9 and 28.5+ months. All who did not respond favorably died within 8 months. During the infusion of BCNU, complications included transient orbital and head pain, periorbital and scleral erythema in all patients, and a focal seizure in 1 (4%). During the 6-month induction periods, leukopenia and thrombocytopenia occurred in 1 (4%), deep vein thrombosis occurred in 9 (36%), pulmonary emboli occurred in 8 (32%), upper respiratory infections occurred in 6 (24%), pneumonia occurred in 9 (36%), and herpes zoster occurred in 1 (4%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraarterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and systemic chemotherapy for malignant gliomas: a follow-up study. 631 73

Alpha and beta interferon were tested for antitumor activity and clinical toxicity in 15 children suffering from cancer. The drug was administered IV, IM, IT or intralesionally daily in the majority of cases in total doses of 18 X 10(6) to 9,634 X 10(5) IU. Major toxicities were a flulike syndrome, elevation of transaminase activity and leukopenia. A minor response (less than 50%) was observed in one patient with glioblastoma, treated by intrathecal administration, and an objective local response was noted in one rhabdomyosarcoma patient with multiple subcutaneous metastases, who was treated by intralesional administration. CNS leukemia in two patients improved without hematological response. Further trials are warranted.
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PMID:[Clinical experience with alpha and beta interferon in childhood cancer]. 659 60

Since 1980, phase 1 and 2 clinical trials of Hu-IFN-beta have been done in the field of neurosurgery. In the present study, (1) the results of in vivo experiments of Hu-IFN-beta are reported and (2) the effectiveness of Hu-IFN-beta in patients with malignant brain tumors is also evaluated. (1) The antitumor activities of beta-IFN and poly ICLC in nude mice receiving subcutaneous transplants of human brain tumors (2 strains) were compared with those of conventional anticancer drugs. After 3 weeks of treatment with ACNU, vincristine, bleomycin, mitomycin C, beta-IFN and poly ICLC, tumor reduction rates were evaluated by the method of Battelle. The effectiveness of beta-IFN and poly ICLC was slightly inferior to that of ACNU and vincristine, although tumor reduction rates (treated/control values) of 43% and 39% were respectively obtained with beta-IFN and poly ICLC against one strain of glioblastoma. (2) Clinically, 7 patients with malignant brain tumors were given beta-IFN (4 by intratumor administration and 3 by intravenous injection) in a dose of 3 X 10(6) to 9 X 10(6) IU/day for 2 to 6 months to study the efficiency and side effects of IFN treatment. One of four patients given IFN intratumorally showed a reduction in tumor size (partial response) by CT scan; the three patients injected IFN intravenously were unchanged. There were no noteworthy side effects in the cases treated intratumorally except for fever occurring in one patient. In the patients treated intravenously, however, fever, general malaise, leukopenia and thrombocytopenia were noted.
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PMID:[Effect of human fibroblast interferon on malignant brain tumors]. 665 89

Interferon inducing activity, antitumor activity and toxicity of poly ICLC (poly IC stabilized with poly L-Lysine and carboxymethyl cellulose) in rodents were studied. SD strain rats were injected intravenously with poly IC or poly ICLC. Interferon in rat plasma was assayed by a plaque reduction method using stomatitis virus. The peak level of plasma interferon of the poly ICLC injection rat was as high as that of poly IC injection rat, and in the former, high level of plasma interferon persisted for 4-12 hours. Next, brain tumor-bearing rats were treated intravenously with poly ICLC and observed for death daily. Weekly treatment with 1 mg/kg of poly ICLC increased the mean survival time although no antitumor effect was observed with poly IC. The LD 50 value of poly IC was 33.5 mg/kg, and that of poly ICLC was 18.6 mg/kg and as to poly ICLC administration, no remarkable side effect was recognized below the dose of 1.5 mg/kg. In clinical trials, poly ICLC was given intravenously at the dose of 0.05-0.2 mg/kg to 9 patients with malignant brain tumor. (6 patients were glioblastoma, 1 was astrocytoma, and 2 were ependymoma.) In 2 patients, poly ICLC was administered once, in 2 patients twice, in 2 patients 3 times, and in 3 patients more than 5 times. The interval of each administration was 7 days. Poly ICLC induced high level of serum interferon (more than 100 reference unit/ml) in all patients and over 100 unit/ml of interferon was maintained for 24 hours. The highest interferon titer induced was 875 unit/ml. The most frequently encountered toxic reaction was fever, which occurred in all cases. The mean peak temperature elevation was 1.9 degrees C, which usually occurred 4-8 hours after drug administration. Modest hypotention was detected in one case. Leucopenia was detected in 3 cases. These abnormalities were all modest, and improved in a few days. As to the effect of poly ICLC, neurological improvement was recognized in 3 cases, and in one of them, remission on CT scan was also recognized.
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PMID:[Effect of interferon inducer (poly ICLC) in the treatment of malignant brain tumor (author's transl)]. 709 65

KRN8602(MX2) is a newly developed morpholino-anthracycline that has been found to cross the blood-brain barrier and be distributed in brain tissue after intravenous administration and to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo. In order to confirm these promising preclinical observations clinically, we performed a phase II trial of KRN8602 in patients with recurrent malignant glioma. The 44 patients enrolled received at least 2 cycles of KRN8602 35 mg/m2/day at 3-4 week intervals by intravenous bolus. Of the 44 patients, 37 could be evaluated for response, and 39 for toxicity. One patient with anaplastic astrocytoma had a complete response (1/37, 3%), and 2 patients with anaplastic astrocytoma and 1 with brain stem glioma had a partial response (3/37, 8%). The overall response rate was 11% (4/37). All patients who responded had received prior chemotherapy that included nitrosoureas. No response was observed in the patients with glioblastoma. Myelosuppression was moderately severe, with 72% of patients developing grade 3 or 4 leukopenia. Severe nausea/vomiting was observed in 31% of the patients. No severe cardiotoxicity was observed. The results indicate that KRN8602 has modest activity against recurrent malignant glioma with relatively severe, but manageable toxicity. It seems to be worthwhile to further assess the efficacy and toxicity of KRN8602 against malignant glioma, which is generally less sensitive to chemotherapy.
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PMID:A phase II study of KRN8602(MX2), a novel morpholino anthracycline derivative, in patients with recurrent malignant glioma. 1042 Oct 76

KRN8602 (MX2) is a newly developed morpholino anthracycline that crosses the blood-brain barrier where it becomes distributed in brain tissue after intravenous administration. This morpholino anthracycline has been found to be effective against human glioma cells and the intracerebrally transplanted tumors in vivo, We performed a phase II trial using KRN8602 as a single agent in malignant glioma patients who had not received prior adjuvant therapy. The 13 patients (5 glioblastomas, 7 anaplastic astrocytomas and 1 malignant oligodendroglioma) enrolled received at least 1 cycle of KRN8602 at 35 mg/m2/day in 3-4 week intervals by intravenous bolus. Ten of these patients could be evaluated for response, and 13 for toxicity. Three patients (1 glioblastoma and 2 anaplastic astrocytomas) demonstrated a complete response (3/10, 30%). Concerning side effects, myelosuppression was moderately severe, with 30.7% of patients developing grade 3 leukopenia. Severe nausea/vomiting was observed in 69% of the patients, however, cardiotoxicity was not observed. The results indicate that KRN8602 demonstrated modest activity against malignant glioma with relatively severe, but manageable toxicity. Further assessment of the efficacy and toxicity of KRN8602 against malignant glioma may be worthwhile.
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PMID:Phase II trial of pre-irradiation KRN8602 (MX2) in malignant glioma patients. 1108 79


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