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

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

Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol and ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 micrometer and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied.
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PMID:Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. 981 94