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)

Sequential administration of VM 26 and CCNU has been used in France for the treatment of glioblastoma since 1973. Results have shown that this association can cause a remission lasting, on average, from seven to eight months after starting chemotherapy. It seems that, adding Adriamycin to this sequential therapy does not increase its efficiency. On the other side, dosage and the interval between cycles of chemotherapy appear to be a determining factor in the activity, but the limits are very narrow. Therapy is either ineffective or has doubtful efficiency in about one third of patients, and even when prolonged clinical remission is obtained, cessation of therapy, usually due to a persistent thrombopenia is followed by progression of the tumour in the following months. The large amount of research being made in the field of cellular kinetics and pharcacology will, hopefully, lead to improvement in results.
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PMID:[A study of the use of sequential chemotherapy in 176 cases of glioblastoma (author's transl)]. 36 92

Fifteen patients were treated in a Phase I study of intracarotid carboplatin (200-400 mg/m2) in 5% dextrose and water infused over 15 to 30 minutes through a transfemoral catheter with a 0.2-micron inline filter. This study was done because intravenous carboplatin has less neurotoxicity than cisplatin and is active against brain tumors. Eleven men and four women ranging in age from 37 to 72 years (median, 59 years) were treated. The Eastern Cooperative Oncology Group performance status was 1 in 3, 2 in 4, and 3-4 in 8 patients. Eight patients had one to three previous chemotherapy regimens; previous radiotherapy had failed in 13 patients. The response of patients in the Phase I study follows: glioblastoma, 6 failed; not evaluated because of early death from pulmonary embolus, 1; recurrent Grade II and III glioma, 1 stable (minor response with neurologic improvement) and 2 failed; malignant oligodendroglioma, 1 failed; brain metastases from nonsmall cell lung cancer, 1 partial remission, 1 stable (minor response), and 1 failed; brain metastases from unknown primary, 1 stable (minor response with neurological improvement). Median survival was 9 weeks. Nausea was mild to moderate. One patient had granulocytopenia, and 2 had thrombocytopenia (mild). At 200 mg/m2 (2 patients), 1 had a focal seizure. At 300 mg/m2 (9 patients), 2 with abnormally small arteries had severe pain early in the treatment and posttreatment ipsilateral conjunctival edema, decreased vision, and cerebral edema (with partially reversible increased hemiparesis); 1 other had mild decrease in ipsilateral vision and 1 had transient aphasia on removal of the catheter (possibly the result of a vascular spasm).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of intracarotid administration of carboplatin. 131 64

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.
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PMID:Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies. 133 50

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.
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PMID:Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer. 139 37

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

As previously reported, cytotoxic synergy is produced when clinically achievable concentrations of cytarabine (Ara-C) and hydroxyurea (HU) are used as potential inhibitors of in vitro DNA repair in cisplatin (cis-Pt)-treated human colon carcinoma cells. This pilot study was subsequently designed to duplicate the in vitro dose and schedule and to determine the toxicity of this three-drug combination in two cohorts of patients. 21 patients had received prior chemotherapy and 19 were not previously treated. All patients had refractory solid tumors. They received monthly cycles of an oral loading dose of 800 mg/m2 HU followed every 2 h by 6 oral doses of 400 mg/m2, a 12-h continuous infusion of 200 or 250 mg/m2/h Ara-C concurrent with the HU, and then 100 mg/m2 cis-Pt over 1 h. A total of 95 cycles were given with the expected toxicities of nausea and vomiting and fatigue but not major acute toxicity observed. Thrombocytopenia was significant but transient and was dose-limiting only for patients who had received prior therapy. The median platelet nadir after one cycle was 43,000/microliters for all patients and 67,000/microliters for those who had not undergone prior treatment. Azotemia was treatment-limiting in responding and stable patients, suggesting the possibility of synergistic nephrotoxicity. Interestingly, there were early transient rises in both uric acid and lactate dehydrogenase (LDH). Partial responses were seen in 9 of 32 patients with measurable disease and there was significantly improvement in 5 of 8 patients with only evaluable disease. The responses or improvement occurred in patients with non-small-cell lung cancer, breast carcinoma, glioblastoma, ovarian carcinoma, small-cell lung cancer, and mesothelioma. Of these 14 patients, 9 had failed prior chemotherapy regimens. Significantly, responses were observed in 3 of 8 patients who had previously received cis-Pt, suggesting that the HU/Ara-C combination modulated cis-Pt resistance. Because of these encouraging results, a second pilot study has been initiated with modifications dictated by the toxicity issues raised in this trial.
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PMID:Cisplatin preceded by concurrent cytarabine and hydroxyurea: a pilot study based on an in vitro model. 224 91

The therapeutic potential of interleukin 1 (IL-1) in the treatment of malignant glioma was investigated. The direct effect of recombinant human IL-1 beta (rHuIL-1 beta) on cultured U-373 MG glioma cell was evaluated in vitro by BrdU uptake assay, and these effects were compared with those of human interferon beta (HuIFN-beta). Though a growth inhibition and an increase of the percentage of process bearing cells were observed with rHuIL-1 beta at a concentration of 100 ng/ml, these in vitro effects of rHuIL-1 beta were less than those of HuIFN-beta at the same concentrations. Prevention of and enhanced recovery from myelosuppression caused by ACNU by rHuIL-1 beta were evaluated in BALB/c mice. Intravenous injection of ACNU at a dose of 60 mg/kg caused marked decreases in the number of leukocytes, neutrophils, reticulocytes and thrombocytes after seven days. Pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single i.p. injection had a significant preventive effect on these myelosuppression including thrombocytopenia. Enhanced recovery by rHuIL-1 beta administrated seven days after injection of ACNU was also observed. Experimental combination immunochemotherapy with ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. More than 60 mg/kg of ACNU given intraperitoneally inhibited the growth of human glioblastoma in nude mice, but had no effect on survival time of nude mice. The antitumor effect of ACNU was significantly augmented by coadministration of 1 microgram/mouse rHuIL-1 beta. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of ACNU with rHuIL-1 beta. These results suggest that the combined use of IL-1 with chemotherapeutic agents seems to be desirable for clinical application in the treatment of patient with malignant gliomas from the viewpoints of the direct anti-tumor effect, the enhancement of the host immunity, and the prevention of myelosuppression caused by those agents.
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PMID:[Application of interleukin 1 in the treatment of malignant gliomas with special reference to the experimental combination therapy with ACNU]. 235 Jan 91

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 I study of the intracarotid administration of PCNU was conducted in patients with intracerebral tumors recurring after cranial radiation. Seventeen patients were treated including 16 with recurrent gliomas or glioblastomas and 1 with recurrent brain metastases from adenocarcinoma of the lung. An additional patient received a vertebral artery infusion of PCNU for a recurrent glioblastoma. Seven of 17 patients receiving intracarotid PCNU responded for a response rate of 41%. If only evaluable patients with gliomas are considered, the response rate was 44%. Tumor grade at time of initial diagnosis, exposure to prior chemotherapy, and dose of PCNU did not appear to have a major impact on response rate. Zubrod performance status 3 patients had a lower response rate (25%) than did patients with performance status 1 or 2 (response rate 63%). Thrombocytopenia and reversible central nervous system toxicity were dose limiting at a PCNU dose of 110 mg/m2. Two patients had possible permanent central nervous system toxicity. Three patients had permanent ipsilateral visual impairment, including one at the lowest dose used into the carotid artery (60 mg/m2). Orbital pain appeared to be substantially less than that seen with intracarotid BCNU but headaches may have been somewhat more common. The single patient receiving a vertebral artery infusion developed marked headaches and restlessness after receiving 25 mg/m2 of a planned 75 mg/m2 treatment into the vertebral artery and the treatment had to be discontinued. Symptoms were rapidly reversible upon stopping the medication. Our overall impression is that intracarotid PCNU causes less ocular pain but more transient central nervous system toxicity than does intracarotid BCNU.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of intracarotid PCNU. 368 87

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


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