NATIONAL-CANCER-INSTITUTE (PHASE-II) STUDY OF HIGH-GRADE GLIOMA TREATED WITH ACCELERATED HYPERFRACTIONATED RADIATION AND IODODEOXYURIDINE - RESULTS IN ANAPLASTIC ASTROCYTOMA

Purpose: We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). Methods and Materials: Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m(2) per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-dean field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. Results: Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. Conclusion: Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity.