Irinotecan therapy in adults with recurrent or progressive malignant glioma

Purpose: To determine the activity, toxicity, and pharmacokinetics of irino tecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatme nt of adults with progressive, persistent, or recurrent malignant glioma. Patients and Methods: Patients with progressive or recurrent malignant glio mas 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/ m(2) 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 treate d 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 we eks). Toxicity observed during the study was limited to infrequent neutrope nia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under t he plasma concentration-time curves through infinite time valuer in these p atients were approximately 40%, 25%, and 25%, respectively, of those determ ined 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 st arting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low pl asma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone e nhances drug clearance. J Clin Oncol 17:1516-1525. (C) 1999 by American Soc iety of Clinical Oncology.