Combined radiochemotherapy with paclitaxel in the treatment of malignant glioma

Background: Paclitaxel is a radiosensitizing agent that shows a synergistic effect with radiation in malignant glioma cells. A phase I/II trial was performed in order to evaluate both feasibility and outcome of combined radiochemotherapy in malignant glioma. Patients and Methods: 56 patients were included in the trial. Paclitaxel was administered on days 1-4, 15-18 and 29-32 18 to 24 hours prior to irradiation. Radiotherapy with 60 Gy in conventional fractionation was initiated on day 2. 31 patients were included in a dose-escalation trial starting with 20 mg/m2/d and increasing up to 60 mg/m2/d in 10-mg steps. Additional 25 patients were treated with 50 mg/m2/d. Results: The regimen was very well tolerated with minimal subjective impairment such as sickness or weakness. Maximal tolerable dose was 50 mg/m2/d, with neutropenia being the dose-limiting toxicity. There were four allergic reactions and five thromboembolisms; furthermore, one patient with a normal blood count died due to pneumonia. The median survival was 12 months, and significantly favorable factors were a young age, a lower tumor grade (grade 3) and a complete resection. Varying the paclitaxel dose had no influence on outcome. Conclusions: Combined radiochemotherapy with paclitaxel in the treatment of malignant glioma was well tolerated. Maximal tolerable dose was 50 mg/m2/d. There was no increase in survival compared with results reported in the literature. (orig.)