Irinotecan therapy in adults with recurrent or progressive malignant glioma.


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.

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@article{Friedman1999IrinotecanTI, title={Irinotecan therapy in adults with recurrent or progressive malignant glioma.}, author={Henry S . Friedman and William P. Petros and Allan H . Friedman and Larry J. Schaaf and Tracy Kerby and Jennifer Lawyer and Mary Parry and Peter John Houghton and Sonya Lovell and Khawla Rasheed and Timothy Cloughsey and Evelyn S Stewart and O. Michael Colvin and James M. Provenzale and Roger E McLendon and Darell D Bigner and Ilkcan Cokgor and Michael M Haglund and Jeremy Rich and David Michael Ashley and J Malczyn and Gary L. Elfring and Langdon L. Miller}, journal={Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, year={1999}, volume={17 5}, pages={1516-25} }