Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial

Abstract

A prospective randomized trial of 157 patients with malignant astrocytoma (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m2) six weekly and hydroxyurea (HU, 3.5 gm/m2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600-4000 rad in 36-40 fr of 100 rad each, given 4 fr per day at 3-hour intervals over two weeks) Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P less than 0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow-up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimens had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease.