Phase II, two-arm RTOG trial (94-11) of bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 gy) based on tumor volume (> 20 or ≤ 20 CM2, respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients

Purpose: To compare survivorship, and acute and delayed toxicities following radiation therapy (RT) of radiosurgery-ineligible glioblastoma multiforme (GBM) patients treated with tumor volume-influenced, high-dose accelerated, hyperfractionated RT plus bischloroethyl-nitrosourea (BCNU), using prior RTOG malignant glioblastoma patients as historical controls. Methods and Materials: One hundred four of 108 patients accrued from June 1994 through May 1995 from 26 institutions were analyzable. Patients were histologically confirmed with GEM, and previously untreated. Treatment assignment (52 patients/arm) was based on tumor mass (TM), defined as the product of the maximum diameter and greatest perpendicular dimension of the titanium-gadolinium-enhanced postoperative MRI: Arm A, 64 Gy, TM > 20 cm(2); or Arm B, 70.4 Gy, TM less than or equal to 20 cm(2). Both Arms A and B received BCNU (80 mg/m(2), under hyperhydration) days 1-3, 56-58, then 4 cycles, each 8 weeks, for a total of 6 treatment series. Results: During the 24 months immediately post-treatment, the overall median survival was 9.1 months in Arm A (64 Gy) and 11.0 months in Arm B (70.4 Gy), Median survival in recursive partitioning analysis (RPA) Class III/IV was 10.4 months in Arm A and 12.2 months in Arm B, while RPA Class V/VI was 7.6 months in Arm A and 6.1 months in Arm B, There were no grade 4 neurological toxicities in Arm A; 2 grade 4 neurological toxicities were observed in Arm B (1 motor deficit, 1 necrosis at 157 days post-treatment). Conclusion: This strategy of high-dose, accelerated hyperfractionated radiotherapy shortens overall RT treatment times while allowing dose escalation, and it provides the potential for combination with currently available, as well as newer, chemotherapy agents. Survival is comparable with previously published RTOG data, and toxicities are within acceptable limits. (C) 2000 Elsevier Science Inc.