Temozolomide combined with radiation as first-line treatment in primary glioblastoma multiforme: Phase I/II-study

Abstract

1531 Background: The role of chemotherapy in combination with radiation therapy is still discussed controversially in the treatment of primary glioblastoma multiforme. To evaluate the feasibility and toxicity of radiation and concomitant administration of temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. Methods: 53 Patients with histologically confirmed WHO °IV malignant glioma were enrolled in the study. All patients were treated with radiation therapy with a total dose of 60Gy using conventional fractionation of 5x2.0Gy/week. Temozolomide was administered orally each therapy day at a dose of 50mg/m2. Results: Prior to radio-chemotherapy, complete resection of the tumor was performed in 14 patients, 22 patients received a subtotal resection, and in 17 patients only a biopsy could be performed. The median time interval between surgery and initiation of radio-chemotherapy was 21 days. Treatment related toxicity was very mild. Acute toxicity > °II was observed in one patient who developed °IV hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting which could be managed with odansetron medication. No severe late effects were observed. The median progression-free survival and the median overall survival were 8 months and 19 months, respectively. Actuarial overall survival was 72% at 1 year and 29% at 2 years. Age < 40 vs. > 40 and extent of surgery significantly influenced survival. Conclusion: The combination of temozolomide plus radiation therapy is feasible and safe by means of toxicity. Overall survival times were relatively high compared to the survival times reported for radiotherapy alone. By applying a dosage of 50mg/m2of temozolomide, application can be performed throughout the whole time course without interruption due to side effects and might contribute in a large manner to the prolonged overall survival. A clinical phase III trial is warranted to prove the superiority of combined radiotherapy with temozolomide compared to radiotherapy alone. No significant financial relationships to disclose.