Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas

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).

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.

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/m2 every 3 weeks, 3 patients 500 mg/m2, 6 patients 600 mg/m2 and 3 patients 700 mg/m2. 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.

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/m2. 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).

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/m2 every 3 weeks of CPT-11 in patients on AEDs is suggested based on toxicity analysis.