High-dose radiation therapy with low-dose (pulsed) BCNU in malignant gliomas: an Eastern Cooperative Oncology Group (ECOG) report.

Based on preliminary favorable results with the use of postoperative high-dose radiation therapy for malignant gliomas and encouraging experimental studies which indicated that fractionated does of BCNU given 16 hours before irradiation significantly enhanced the effect of radiation both in vitro and in vivo, the Eastern Cooperative Oncology Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of Group (ECOG) decided to explore the use of high-dose radiation therapy in combination with pulsed low doses of BCNU in a high-risk Phase I-II pilot study. The radiation therapy consisted of delivering 6000 rad to the whole brain plus a boost of 1000 rad to the tumor. BCNU was given i.v. 16 hours before the next radiation fraction with doses of 20 mg/M2 twice weekly for six weeks beginning on the second day of irradiation. Twelve patients were treated (5 with Grade III and 7 with Grade IV Astrocytomas). The median survival for the entire group was 80 weeks (30 weeks for Grade IV and 210 weeks for Grade III tumors). These results are not difficult from what was achieved by high-dose radiation alone. Subsequent experimental data seem to indicate that probably the smallest dose of BCNU that should be used in pulsed BCNU combined modality therapy is 80 mg/M2. In general, the treatment as offered in this study was well tolerated. There were no fatal or life-threatening hematologic toxicities and only one patient exhibited a transitory leukopenia of 1600.