A Randomized Trial of Accelerated Hyperfractionated Radiation Therapy and Bis-chloroethyl Nitrosourea for Malignant Glioma. A Preliminary Report of Radiation Therapy Oncology Group 83-02

Background: The third and final randomization of Radiation Therapy Oncology Group (RTOG) 83-02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy (AHRT) in 1.6 Gy twice-daily fractions for adult malignant glioma.

Methods: From December 1987 to July 1989, 304 patients with malignant glioma were stratified by age, performance status, and histologic findings and randomized to receive total AHRT doses of 48.0 or 54.4 Gy, with 80 mg/m2 of bis-chloroethyl nitrosourea (BCNU) for 3 days every 8 weeks. Distribution of other prognostic factors, including neurologic function, extent of surgery, tumor size, and sex, was comparable in each treatment arm.

Results: One Grade 5 radiation therapy (RT)-related toxic effect was reported (in the 54.4-Gy treatment arm), and the incidence of late Grade 3-5 RT-related toxic effects at 18 months was 1% at 48.0 Gy and 4% at 54.4 Gy. The median survival times (MST) for the 48.0 Gy and 54.4 Gy treatment arms were 11.7 and 10.8 months, respectively, comparable to the MST in prior RTOG trials with a similar proportion of patients with glioblastoma multiforme (79%). For the 123 patients who were 60 years of age or older, the MST for the 48.0 Gy and 54.4 Gy treatment arms were 8.9 and 10.4 months, respectively, and compare favorably with the MST of 6.0 months reported with standard RT and BCNU treatment used for 101 patients who were 60 years of age or older in two prior RTOG malignant glioma trials (74-01 and 79-18). Although these results differ significantly (P = 0.0015), this contrast is not significant when adjusted by performance status.

Conclusions: The maximum tolerated dose of AHRT has yet to be identified, and pursuit of this information may most benefit patients with malignant glioma who are 60 years of age or older.