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)

Seventeen patients, aged 9 to 63 years (mean age 38.2 years), with 6 recurring malignant glioma, 5 malignant meningioma, 4 metastatic brain tumor, one endodermal sinus tumor and one embryonal carcinoma were postoperatively treated with adriamycin (ADM). As a rule, 20 mg of ADM (to 960 mg in a total dosis) were given by means of intra-carotid administration every two weeks (to 250 months in duration). According to Karnofsky's evaluation, 4 of 6 glioblastoma patients(66.7%), 4 of 5 malignant meningioma (80%), 2 of 4 metastatic brain tumor (50%) and one embryonal carcinoma had improvement of clinical condition, at least during two months after the beginning of the treatment, and/or remission of more than 50% of the enhanced area on CT scan. Consequently, allover response rate was 64.7%. Tumor tissue concentration of ADM administered intraoperatively by the same regimen, was estimated by fluorescence assay, twenty times in sixteen patients. The level of the concentration was higher in malignant tumor (3.6 to 6.2 micrograms/g) than in low grade astrocytoma (1.5 microgram/g in maximum) during sixty minutes after ADM administration. On the other hand, when ADM of same dosis was given intravenously, maximum serum level was 2.8 microgram/ml, which was less than half in comparison with tissue level of intracarotid administration. There was a serious myelosuppression in two cases in our series, but no cardiomuscular damage was observed in any cases. In conclusion, ADM concentration of brain tissue such as malignant meningioma, metastatic brain tumor and, even glioblastoma, was highly obtained. Further, intermittent intra-carotid administration of ADM was more effective than intravenous dripping in treating malignant intracranial tumor, although side effects should be carefully avoided.
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PMID:[Postoperative treatment for malignant intracranial tumors--especially concerning intermittent intra-carotid administration of adriamycin]. 646 30

Seventy-three patients under 18 years of age with a recurrent central nervous system tumor were randomized to receive combination chemotherapy with MOPP or OPP. Patients were stratified according to the tumor type into four major disease categories: (1) medulloblastoma, (2) astrocytoma and other glioma, (3) ependymoma, and (4) miscellaneous tumors to provide equal distribution of patients for each treatment within each disease category. Evaluation of response was based on computerized brain scan findings. Thirty-five patients received MOPP and 38 received OPP treatment. There were three complete and six partial remissions among patients receiving MOPP and one complete and five partial remissions among patients receiving OPP. In addition, six patients on MOPP had stable disease for seven to 21 months. Only two patients on OPP had stable disease(6 and 36 months). Most of responses in both treatment regimens occurred in patients with medulloblastoma and astrocytoma. Median duration of remission was nine months for the MOPP and 11 months for the OPP. Two patients on MOPP regimen had fatal myelosuppression. Although the more toxic MOPP regimen produced more responses than OPP in children, differences in the duration of response or survival were not statistically significant (P = .79 and P = .84, respectively).
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PMID:Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with or without nitrogen mustard (NSC-762)(MOPP vs OPP) in children with recurrent brain tumors. 654 2

2,5-Diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone (AZQ; Diaziquone, NSC 182986) is a rationally designed antitumor drug possessing sufficient lipid solubility to allow penetration into the central nervous system. Thirty-one patients with high-grade glioma and progressive disease following radiation, with or without previous chemotherapy, have been treated with 144 cycles of drug, consisting of 20 mg/sq m given as an i.v. infusion on Days 1 and 8 of a 28-day cycle. Responses were measured by serial computer tomography scanning. Of the 28 evaluable patients, 6 (21%) had limited improvement (10 to 40% reduction in tumor size) on computer tomography scan, 10 (36%) had disease stabilization, and 12 (43%) had progressive disease. The drug was well tolerated clinically, with little acute toxicity. The major toxicity was myelosuppression, which appeared cumulative, using this dose regimen. AZQ was measurable in both tumor tissue and tumor cyst fluid in patients on therapy. Plasma samples taken during the period of infusion confirm that 50% or more of the total AZQ exposure occurs during the infusion period. AZQ behaves as intended by design and demonstrates activity in this poor-prognosis group of patients.
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PMID:Phase II and pharmacokinetic study of aziridinylbenzoquinone [2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone, diaziquone, NSC 182986] in high-grade gliomas. 664 May 49

To evaluate the potential differential effect of pretreatment with pharmacologic doses of the trace element zinc on the chemosensitivity of glioma cells and bone marrow cells for carmustine (BCNU), we performed in vitro and in vivo studies of zinc toxicity as well as of the combined treatment with zinc and the anticancer drug. We studied the in vitro effects on established human and rat glioma cell lines using a microcolorimetric growth assay and on murine bone marrow using a clonogenic assay for committed progenitor cells of the granulocyte-monocyte lineage. Zinc exposures of up to 100 microM for 120 h did not influence the growth of six of seven human glioma cell lines. Only U87MG demonstrated statistically significant toxicity during high zinc exposure (100 microM over 120 h). Dose-response growth curves generated for BCNU did not show protection against the anticancer agents by a 48-h pretreatment with different zinc concentrations. The clonogenic capacity of bone marrow cells was slightly reduced by in vitro culture for 24 and 48 h. Although this effect appeared to be more prominent in the presence of zinc supplementation, overall a statistically significant inhibition was seen only after exposure to a concentration of 100 microM zinc over 48 h. As compared with chemotherapy alone, in vitro pretreatment with 50 microM zinc over 48 h followed by chemotherapy resulted in an increased number of colony-forming unit-granulocyte monocyte (CFU-GM): CFU-GM increased by a factor of 2 for BCNU (60 microM x 2 h). This statistically significant in vitro chemoprotection would translate into a dose-protection factor of 1.5, i.e., for the same level of myelosuppression, zinc pretreatment would allow administration of a 50% increased dose of BCNU. The in vivo studies were performed in an s.c. xenograft model of the human glioma cell line U87MG in athymic mice. The maximal tolerable pretreatment with zinc was determined to be a 10-day course of daily i.p. injections of 10 mg/kg ZnCl2. The subsequent i.p. administration of the dose lethal to 10% of the mice (LD10) and of a 1.5 x LD10 dose of BCNU resulted in less bone marrow toxicity in pretreated animals than in non-zinc-pretreated mice as determined in a CFU-GM assay. Glioma colony-forming efficiency (CFE) assays, on the other hand, did not show any zinc-related difference in the BCNU sensitivity of U87MG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of pharmacologic doses of zinc on the therapeutic index of brain tumor chemotherapy with carmustine. 752 Aug 43

Amonafide, a novel imide derivative with broad preclinical antitumor activity, achieves significant cerebrospinal fluid levels in animal models. In order to test its antitumor activity in patients with recurrent diffuse infiltrative glioma of the astrocytic and oligodendroglial type, we performed a phase II clinical trial. Of the 22 eligible and evaluable patients treated, 2 (9%) experienced tumor regression lasting more than one year. No other patients experienced tumor regression; one remained stable more than six months. Toxicities consisted primarily of myelosuppression, vomiting, and venous irritation at the infusion site. We conclude that amonafide has minimal activity in recurrent glioma patients. Further investigations are not warranted in this study population.
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PMID:Phase II study of amonafide in patients with recurrent glioma. 762 74

Piritrexim is a lipid-soluble drug which is as effective an inhibitor of dihydrofolate reductase as methotrexate. Phase I and II studies have indicated activity in some tumour types. Because of its lipophilicity we have conducted a phase II study in recurrent high-grade malignant glioma (grades III and IV). Twenty-seven patients were treated with 25 mg p.o. three times daily for five consecutive days, repeated weekly, with provision for dose escalation or reduction according to toxicity. Five patients received less than 4 weeks' treatment because of disease progression or death. Twenty-two patients were evaluable for response. One complete and one partial response was seen (duration 262+ and 241+ weeks) and 13 patients had static disease for a median duration of 13 weeks (range 7-35). The major toxicity was myelosuppression. This response rate of 9% of evaluable patients is much lower than that seen for some conventionally used drugs and we conclude that piritrexim is unlikely to be of value in the management of high-grade gliomas.
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PMID:A phase II study of oral piritrexim in recurrent high-grade (III, IV) glioma. 766 91

Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.
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PMID:[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas]. 775 90

The effects of a combination of simvastatin, a cholesterol-lowering agent, and carmustine (BCNU; N,N'-bis(2-chloroethyl)-N-nitrosourea) on experimental C6 glioma were studied in vitro and in vivo. In vitro simvastatin and BCNU alone inhibited cell proliferation in a dose-dependent fashion. A subliminal concentration of simvastatin (0.1 microM) markedly and synergistically increased the BCNU toxicity to C6 glioma cells. The cytofluorimetric analysis of DNA from simvastatin-treated C6 glioma cells showed, besides the already described arrest in G1, an arrest/retardation in G2-M. Mitotic index from C6 cells incubated with simvastatin (10 microM) decreased by about 90%, indicating a specific C6 arrest/retardation in G2. The drug effects could be completely reversed by simvastatin withdrawal or mevalonate addition to the cultured cells. The combination of simvastatin and BCNU resulted predominantly from the profound retardation of cells in the G2-M compartment of the cell cycle. In vivo simvastatin (administered daily mixed with food) and BCNU (single i.p. injection), when given separately, caused a dose-dependent inhibition of labeling index in C6 glioma homografts (ID50, 61 mg/kg/day and 8.7 mg/kg, respectively). The combination of the lowest doses tested (simvastatin, 25 mg/kg/day and BCNU 0.3 mg/kg) resulted in a significant growth delay (compared to either drug alone) in C6 glioma (P < 0.05). There was no significant increase in toxicity as assessed by myelosuppression (WBC counts and bone marrow labeling index) and body weight. The results provide in vivo support for the combined use of simvastatin, a cholesterol-lowering agent, and BCNU in brain tumor treatment.
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PMID:In vivo enhanced antitumor activity of carmustine [N,N'-bis(2-chloroethyl)-N-nitrosourea] by simvastatin. 783 30

The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-alpha) in patients with recurrent glioma. As single agents, both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-alpha 2a (12 x 10(6) U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-alpha and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-alpha is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial.
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PMID:Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma. 786 Dec 21

Fotemustine is a new chloroethylnitrosourea characterized by the grafting of a phosphonoalanine group onto a nitrosourea radical. Clinical studies using fotemustine have been conducted in malignant glioma, brain metastasis of non-small cell lung cancer, and disseminated malignant melanoma. In recurrent malignant glioma, fotemustine has been used as a single agent: assessed by computed tomography scan, after 8 weeks, the objective response rate was 26.3% among 38 evaluable patients. Median duration of response was 33 weeks. The main toxicity was hematological (thrombocytopenia and leucopenia). A trial with high-dose fotemustine and autologous bone marrow rescue in newly diagnosed glioma was conducted in 26 patients, and 6 showed a partial response. The median overall survival was approximately 11 months. Myelosuppression was noted in all patients except 1, and other toxicity reported was central nervous system toxicity and epigastric pain. Combined with radiotherapy in 55 patients, a 29% response rate was observed, and this combination was well tolerated and easily manageable on an outpatient basis. Finally, fotemustine has been used intraarterially, with 10 objective responses observed among 26 evaluable patients. In brain metastases of non-small cell lung cancer, fotemustine proved to be active with a response rate of 16.7%. Combined with cisplatinum, fotemustine is still under study, but preliminary results are promising. In cerebral metastases of disseminated malignant melanoma, fotemustine has been evaluated in a total of 140 patients in the various studies: median response rate is 24.3%, ranging from 8.3% to 60.0%. Fotemustine appears to be a good candidate in the treatment of primary brain tumors and metastases.
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PMID:Fotemustine in the treatment of brain primary tumors and metastases. 803 64


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