A Phase III comparison of BCNU, hydroxyurea, and radiation therapy to BCNU and radiation therapy for treatment of primary malignant gliomas

Abstract

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 i.v. for 3 consecutive days before the initiation of radiation therapy, and at 8 wk 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 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 .gtoreq. 60 did better on both arms of the study, with median times to tumor pregression (MTP''s) of 50 and 72 wk for BHR and BR, respectively. GM patients showed statistically significant differences (P = 0.03) between the 2 arms of the study, with MTP of 41 and 31 wk for BHR and BR, respectively. The GM patients with subtotal tumor resection did slightly better on BHR than on BR, with MTP of 49 wk (P = 0.03) and 31 wk for the respective groups.