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 chemotherapy to explore feasibility and toxicity of such combined modality treatment. Methods and Materials: There were 34 males and 14 females with a median age of 53 years (range, 32–74 years) and median Eastern Cooperative Oncology Group performance status score of 1 (range, 0–3). Histology included anaplastic astrocytoma in 11 patients and glioblastoma multiforme in 37 patients. Radiation was given at 1.2 Gy per fraction, two fractions per day, for a total dose of 72 Gy, with a reduction in field size after 52.8 Gy. Four weeks after completion of hyperfractionated radiation therapy multiagent chemotherapy was introduced with bis-chlorethyl 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 cisplatin 20 mg/m 2 , days 1–3. Cycles were repeated every 4 weeks to a maximum 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, interfraction interval and location of tumor influenced survival in glioblastoma multiforms patients on univariate analysis: Patients treated with shorter intervals (4.5 – 5 h) did better than those treated with longer intervals (5.5–6 h); also, glioblastoma multiforme patients with frontal tumors did better than those with tumors of the other locations. Multivariate analysis confirmed that the performance status, interfraction interval, and tumor location were significant prognostic factors in glioblastoma multiforme patients. Acute toxicity was mild. No cases of brain necroses were observed. Conclusion: Hyperfractionated radiation therapy followed by multiagent chemotherapy was well tolerated with mild acute and virtually no late toxicity. More patients and longer follow-up are needed for further evaluation of its activity and late effects in anaplastic astrocytoma patients.