HYPERFRACTIONATED RADIATION-THERAPY (HFX RT) FOLLOWED BY MULTIAGENT CHEMOTHERAPY (CHT) IN PATIENTS WITH MALIGNANT GLIOMA - A PHASE-II STUDY

Purpose: Forty-eight patients with malignant glioma were treated with hyperfractionated radiation therapy followed by multiagent chemotherap y to explore feasibility and toxicity of such combined modality treatm ent. Methods and Materials: There were 34 males and 14 females with a median age of 53 years (range, 32-74 years) and median Eastern Coopera tive Oncology Group performance status score of 1 (range, 0-3). Histol ogy included anaplastic astrocytoma in 11 patients and glioblastoma mu ltiforme in 37 patients. Radiation was given at 1.2 Gy per fraction, t wo fractions per day, for a total dose of 72 Gy, with a reduction in h eld size after 52.8 Gy. Four weeks after completion of hyperfractionat ed radiation therapy multiagent chemotherapy was introduced with bisch lorethyl nitrosourea (BCNU) 50 mg/m(2), days 1-3, vincristine 1.4 mg/m (2) (max. 2 mg), day 1, procarbazine 50 mg/m(2), days 1-7 and cisplati n 20 mg/m(2), days 1-3. Cycles were repeated every 4 weeks to a maximu m of six cycles or until tumor progression was noted. Results: Median survival time for all patients was 52 weeks (range, 16-185 weeks) and median time to tumor progression was 30.5 weeks (range, 12-131 weeks). Besides age, histology, performance status, and extent of surgery, in terfraction interval and location of tumor influenced survival in glio blastoma multiforms patients on univariate analysis: Patients treated with shorter intervals (4.5-5 h) did better than those treated with lo nger intervals (5.5-6 h); also, glioblastoma multiforme patients with frontal tumors did better than those with tumors of the other location s. Multivariate analysis confirmed that the performance status, interf raction interval, and tumor location were significant prognostic facto rs in glioblastoma multiforme patients. Acute toxicity was mild. No ca ses of brain necroses were observed. Conclusion: Hyperfractionated rad iation therapy followed by multiagent chemotherapy was well tolerated with mild acute and virtually no late toxicity. More patients and long er follow-up are needed for further evaluation of its activity and lat e effects in anaplastic astrocytoma patients.