Phase II study of nimustine, carboplatin, vincristine, and interferon-β with radiotherapy for glioblastoma multiforme:: experience of the Kyoto Neuro-Oncology Group

Object. This Phase II study was performed to determine the safety, tolerability, and efficacy. of combining nimustine (ACNU)-carboplatin-vincristine-Interferon-beta (IFN beta) chemotherapy. Methods. Ninety-seven patients with Kamofsky Performance Scale scores of 50 or greater were enrolled in the study. Nimustine (60 mg/m(2)), carboplatin (110 mg/m(2)), vincristine (0.6 mg/m(2)), and IFN beta (10 mu g) were administered on Day 1 concomitant with radiotherapy (63 Gy); vincristine (0.6 mg/m(2)) and IFN beta (10 mu g) on Days 8 and 15; and IFN beta alone (10 pg) three times per week throughout the course of radiotherapy. Fifty-six days after radiotherapy ended, the time schedule for chemotherapy was reset and ACNU, carboplatin, vincristine, and IFNP were again administered on the new Day 1 and vincristine and IFN beta on the new Days 8 and 15. This course was repeated every 56 days. Instances of nonhernatological toxicity were rare and mild. During the course of radiotherapy, the percentages of patients who experienced Grade 3 toxicity were 14% with neurocytopenia and 7% with thrombocytopenia. Seven percent of all adjuvant chemotherapy cycles following radiotherapy were associated with Grade 3 toxicity, as manifested in neurocytopenia or thrombocytopenia. No instance of Grade 4 toxicity was observed. The median duration of progression-free survival was 10 months (95% confidence interval [CI] 8-12 months) and the median duration of overall survival was 16 months (95% CI 13-20 months). Conclusions. The combination of ACNU-carboplatin-vincristine-IFNP chemotherapy and radiotherapy is safe and well tolerated, and may prolong survival in patients with glioblastoma multiforme.