The purpose of this study was to determine the response to
CPT-11 administered every three weeks to adults with progressive
malignant glioma, treated with or without
enzyme-inducing
antiepileptic drug (EIAED)
therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic
glioma (AG) or grade IV
glioblastoma multiforme (GBM) were eligible. No more than one prior
chemotherapy was allowed, either as adjuvant
therapy or for recurrent disease. The
CPT-11 dose was 350 mg/m(2) i.v. every three weeks in patients not on EIAED and 750 mg/m(2) in patients on EIAED
therapy. Patients with stable or responding disease could be treated until
tumor progression or a total of 12 months of
therapy. The primary end point of the study was to determine whether
CPT-11 could significantly delay
tumor progression, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 17.6%. PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included
diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of
CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.