Accelerated radiotherapy with concomitant ACNU/Ara-C for the treatment of malignant glioma

Purpose To evaluate activity and toxicity of simultaneous ACNU and Ara-C wi th concurrent accelerated hyperfractionated radiotherapy in the treatment o f high-grade glioma. Patients and Methods Thirty patients aged 23-71 years (median 47.5), 16 pat ients with glioblastoma multiforme (GBM) and 14 patients with grade-III gli oma, received 93 courses of ACNU/Ara-C (median 4 courses) at following dose levels (ACNU/Ara-C in mg/m(2)/day): 70/90 (11 courses), 75/100 (36 courses ) and 90/120 (46 courses). ACNU was administered IV on day 1 of each cycle, Ara-C as a 2 h-intravenous infusion on days 1-3. Patients received concomi tant radiation therapy with 2 daily fractions of 1.75 Gy up to 57 Gy (media n). Results Median survival of all patients was 13 months, 11 months for GBM an d > 28 months for grade-III glioma; 31% (9 patients) survived longer than 2 4 months. The percentage of grade IV hematological toxicity was dose-depend ent: 33% at the 70/90 dose level, 40% at 75/100 and 58% at 90/120. Six pati ents required platelet transfusion, 1 patient red blood cells; no febrile n eutropenia occurred. Among 18 patients evaluable for response, 3 (17%) show ed PR, 8 (44%) NC and 7 (39%) PD at completion of chemoradiation. No acute or late neurological toxicity occurred in this study. Younger age (p = 0.00 01) and grade-III histology (p = 0.0009) were important prognostic factors for prolonged survival. Conclusion This chemoradiation regimen is active in malignant gliomas and c an be safely recommended at a dose level using 70 mg/m(2) ACNU together wit h 90 mg/m(2) Ara-C.