Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients.

The purpose of this study was to evaluate safety and efficacy of Procarbazine (PCB) and fotemustine (FTM) combination in the treatment of pre-temozolomide treated, recurrent GBM patients. The primary end-point was progression free survival at 6 months (PFS-6). Secondary end-points were overall survival, response rates (CR + PR) and toxicity. About 54 patients (41 men and 13 women) aged 26-68 years (median age, 53.5 years) with recurrent GBM were treated. PCB was administered as an oral dosage of 450 mg on days 1-2 and a total dose of 300 mg on day 3. FTM was administered on day 3, 3 h after the last PCB intake at a dose of 110 mg/mq/BSA. The treatment was repeated every 5 weeks. Treatment was continued for a maximum of six cycles or until disease progression. After two cycles of chemotherapy: 6 patients (11.2%) experienced a neuroradiographic partial response (PR), 29 patients (53.7%) had stable disease (SD), and 19 patients (35.1%) had progressive disease (PD). For the whole group of patients, the median PFS was 19.3 weeks (95% CI, 14.1-24.4 weeks), and PFS-6 was 26.7% (95% CI, 10.6-42.8%). Overall MST from the beginning of PCB + FTM chemotherapy was 28.7 weeks (95% CI, 24.8-32.7 weeks). At 6 and 12 months, 64.4% (95% CI, 51.5-77.3%) and 23.6% (95% CI, 10.1-37.1%) of patients were alive. The median survival time calculated from the first diagnosis was 20.8 months (95% CI, 16.7-24.8). We concluded that the PCB + FTM combination as done in the current trial for patients with recurrent GBM after treatment with TMZ showed some benefit with regards to increased survival and that a Phase III trial is warranted.