Open-label simultaneous radio-chemotherapy of glioblastoma multiforme with topotecan in adults

Background: Due to its radioresistance, the prognosis of glioblastoma multiforme (GBM) remains poor. Therefore, we investigated the impact of simultaneous radio-chemotherapy with topotecan (Hycamtin (R)) on clinical outcome, tolerability and quality of life. Patients and methods: In this multicenter trial, 60 patients (19 females, 41 males) with histologically proven (5 x biopsy, 31 x subtotal resection, 24x total resection) GBM were included. Radio-Chemotherapy was performed with daily doses of 2.0 Gy (total, 60 Gy), and 0.5 mg (absolute dose) of topotecan intravenously 1 h prior to irradiation. Toxicity was assessed using common toxicity criteria (CTC). General condition and quality of life were assessed at baseline, at the end of therapy, and 6 weeks post-therapy. Local control and length of survival were compared with an historical control group of 67 patients only treated with postoperative radiotherapy following stereotactic biopsy (15 x), subtotal resection (39 x), or total resection (13 x). Results: 57 patients completed the therapy. Median radiation dose was 60Gy (range 16-76Gy). Median cumulative topotecan dose was 15 mg (range 7.5-18.5 mg). CTC toxicity grade 3 was observed in six patients and grade 4 toxicity in two patients (three events). Two patients died of septic disease. Mean Karnofsky index was 87% at baseline, 81% at the end of therapy, and 80% at 6 weeks post-therapy. Median survival time was 15 months, significantly longer than the 11 months seen in the control group (P < 0.002). Extent of tumour resection or patient age did not have a significant effect on survival. Conclusion: This multimodal approach is well tolerated, and quality of life remains preserved. The relatively long median survival time is promising but a further randomised double blind placebo controlled parallel designed clinical trial should be performed to confirm these results. (c) 2004 Elsevier B.V. All rights reserved.