Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas

Objective: A prospective Phase I study designed to establish the maximum tolerated dose and secondarily evaluate response rate to CPT-11 in patients with recurrent oligodendrogliomas (oligos) on anticonvulsant drugs (AEDs). Background: Oligos, which constitute 1-2% for all adult brain tumors, are commonly treated with procarbazine, CCNU and vincristine (PCV) chemotherapy. How to treat oligos that have failed PCV, surgery and radiotherapy is more problematic. Design/Methods: Fifteen patients (age range 24-55 years; gender 10 males; 5 females) with recurrent oligos and on AEDs were treated prospectively with CPT-11. Four cohorts of patients defined by CPT-11 dose were treated. Three patients were treated with 400 mg/m(2) every 3 weeks, 3 patients 500 mg/m(2), 6 patients 600 mg/m(2) and 3 patients 700 mg/m(2). Neuroradiographic evaluation was performed after every other dose of CPT-11. In patients with stable or responding disease, two further doses of CPT-11 were administered. Alternative or supportive care was offered to patients with disease progression. Results: Toxicity included neutropenia (3 patients; 1 each with Grade III and Grade IV toxicity); thrombocytopenia (2 patients; 1 with Grade IV toxicity); abdominal pain with or without diarrhea (5 patients; 1 with Grade III toxicity) nausea/vomiting (4 patients). No patient required hospitalization nor did a treatment-related death occur. One patient required a platelet transfusion. Toxicity was a function of CPT-11 dose and the maximum tolerated dose was 600 mg/m(2). Cycles (2-12) of CPT-11 were administered (median 4). Response was as follows: partial response (2 patients); stable disease (5 patients); and progressive disease (8 patients). Duration of response ranged from 1.5 to 9 months with a median of 3. In patients with either stable disease or a partial response, response duration was 4.5-9 months (median 6 months). Progression-free survival at 6 months was 33% and 0% at 12 months. Overall survival following initiation of CPT-11 ranged from 2 to 12 months (median 3 months). In patients with either stable or responding disease, median survival was 7 months (range 6-12 months). Conclusion: In this small cohort of patients with recurrent low-grade oligos having been treated previously with PCV and on cytochrome P450 enzyme inducing AEDs, CPT-11 has modest palliative efficacy and acceptable toxicity. A dose of 600 mg/m(2) every 3 weeks of CPT-11 in patients on AEDs is suggested based on toxicity analysis.