Irinotecan therapy in adults with recurrent or progressive malignant glioma

Henry S. Friedman, William P. Petros, Allan H. Friedman, Larry J. Schaaf, Tracy Kerby, Jennifer Lawyer, Mary Parry, Peter J. Houghton, Shelley Lovell, Karima Rasheed, Tim Cloughsey, Elizabeth S. Stewart, O. Michael Colvin, James M. Provenzale, Roger E. McLendon, Darell D. Bigner, Ilkcan Cokgor, Michael Haglund, Jeremy Rich, David AshleyJoseph Malczyn, Gary L. Elfring, Langdon L. Miller

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323 Scopus citations

Abstract

Purpose: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT- 11, Camptosar; Pharmacia and 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 (IV) 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 (5N-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, 5N-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.

Original languageEnglish (US)
Pages (from-to)1516-1525
Number of pages10
JournalJournal of Clinical Oncology
Volume17
Issue number5
StatePublished - May 1 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Friedman, H. S., Petros, W. P., Friedman, A. H., Schaaf, L. J., Kerby, T., Lawyer, J., Parry, M., Houghton, P. J., Lovell, S., Rasheed, K., Cloughsey, T., Stewart, E. S., Colvin, O. M., Provenzale, J. M., McLendon, R. E., Bigner, D. D., Cokgor, I., Haglund, M., Rich, J., ... Miller, L. L. (1999). Irinotecan therapy in adults with recurrent or progressive malignant glioma. Journal of Clinical Oncology, 17(5), 1516-1525.