Irinotecan therapy in adults with recurrent or progressive malignant glioma.
Published
Journal Article
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.
Full Text
Duke Authors
- Ashley, David
- Bigner, Darell Doty
- Friedman, Allan Howard
- Friedman, Henry Seth
- Haglund, Michael Martin
- McLendon, Roger Edwin
- Provenzale, James Michael
Cited Authors
- Friedman, HS; Petros, WP; Friedman, AH; Schaaf, LJ; Kerby, T; Lawyer, J; Parry, M; Houghton, PJ; Lovell, S; Rasheed, K; Cloughsey, T; Stewart, ES; Colvin, OM; Provenzale, JM; McLendon, RE; Bigner, DD; Cokgor, I; Haglund, M; Rich, J; Ashley, D; Malczyn, J; Elfring, GL; Miller, LL
Published Date
- May 1999
Published In
Volume / Issue
- 17 / 5
Start / End Page
- 1516 - 1525
PubMed ID
- 10334539
Pubmed Central ID
- 10334539
International Standard Serial Number (ISSN)
- 0732-183X
Digital Object Identifier (DOI)
- 10.1200/JCO.1999.17.5.1516
Language
- eng
Conference Location
- United States