Publications [#132115] of James M Provenzale
- HS Friedman, WP Petros, AH Friedman, LJ Schaaf, T Kerby, J Lawyer, M Parry, PJ Houghton, S Lovell, K Rasheed, T Cloughsey, ES Stewart, OM Colvin, JM Provenzale, RE McLendon, DD Bigner, I Cokgor, M Haglund, J Rich, D Ashley, J Malczyn, GL Elfring, LL Miller, Irinotecan therapy in adults with recurrent or progressive malignant glioma.,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 17 no. 5
pp. 1516-25, ISSN 0732-183X
(last updated on 2011/07/12)
OBJECTIVE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. METHODS: Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (i.v.) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients. RESULTS: All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment. CONCLUSIONS: Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance.
Adult • Aged • Antineoplastic Agents, Phytogenic • Astrocytoma • Brain Neoplasms • Camptothecin • Disease Progression • Female • Glioblastoma • Glioma • Humans • Male • Middle Aged • Neoplasm Recurrence, Local • Oligodendroglioma • analogs & derivatives* • blood • drug therapy • drug therapy* • pharmacokinetics • therapeutic use • therapeutic use*