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Irinotecan therapy in adults with recurrent or progressive malignant glioma

journal contribution
posted on 1999-05-01, 00:00 authored by H S Friedman, W P Petros, A H Friedman, L J Schaaf, T Kerby, J Lawyer, M Parry, P J Houghton, S Lovell, K Rasheed, T Cloughsey, E S Stewart, O M Colvin, J M Provenzale, R E McLendon, D D Bigner, I Cokgor, M Haglund, J Rich, David Ashley, J Malczyn, G L Elfring, L L Miller
PURPOSE: 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.
PATIENTS AND 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.
CONCLUSION: 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.

History

Journal

Journal of Clinical Oncology

Volume

17

Issue

5

Pagination

1516 - 1525

Publisher

American Society of Clinical Oncology

Location

Alexandria, Va.

ISSN

0732-183X

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

1999, American Society of Clinical Oncology