✓ This Phase III clinical trial compared the effectiveness of the combination of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), radiation therapy, and hydroxyurea (BHR group) to the combination of BCNU and radiation therapy (BR group) for the treatment of malignant gliomas. In both arms of the study, BCNU was administered intravenously for 3 consecutive days before the initiation of radiation therapy, and at 8-week intervals thereafter until unequivocal tumor progression. In the BHR arm of the study, hydroxyurea was administered orally on alternate days during radiation therapy. Patients in each arm were stratified almost equally by tumor type (glioblastoma multiforme (GM) or other nonglioblastoma multiforme malignant gliomas (NGM)) and extent of surgical resection of tumor. Patients were also evaluated with the Karnofsky Performance Status (KPS) scale. Time to progression was determined by comparing the results of sequential neurological examinations and radionuclide and computerized tomographic scans.
Of the 130 patients entered into the study, 99 constitute the valid study group. Data were analyzed with Kaplan-Meier representations and the statistical methods of Gehan and Cox. The NGM patients with KPS ratings of ≥60 did better on both arms of the study, with median times to tumor progression (MTP's) of 50 and 72 weeks for BHR and BR, respectively. However, GM patients showed statistically significant differences (p = 0.03) between the two arms of the study, with MTP's of 41 and 31 weeks for BHR and BR, respectively. The GM patients with subtotal tumor resection did slightly better on BHR than on BR, with MTP's of 49 weeks (p = 0.03) and 31 weeks for the respective groups.