RESULTS OF A PHASE-II TRIAL OF EXTERNAL-BEAM RADIATION WITH ETANIDAZOLE (SR-2508) FOR THE TREATMENT OF LOCALLY ADVANCED PROSTATE-CANCER (RTOG PROTOCOL-90-20)

Purpose: RTOG Protocol 90-20 was designed to evaluate the effect of th e hypoxic cell sensitizer Etanidazole (SR-2508) on locally advanced ad enocarcinoma of the prostate treated with concurrent external beam irr adiation. Methods and Materials: Patients with biopsy-proven adenocarc inoma of the prostate with locally advanced T-20, T-3, and T-4 tumors were eligible for this study. No patients with disease beyond the pelv is were eligible. Serum prostate specific antigen (PSA) was mandatory. All patients received definitive external beam irradiation using stan dard four-field whole pelvis treatment to 45-50 Gy, followed by a cone down with a minimum total dose to the prostate of 66 Gy at 1.8-2.0 Gy /fraction over 6.5-7.5 weeks. Etanidazole was delivered 1.8 g/m(2) giv en 3 times a week to a total of 34.2 g/m(2) or 19 doses. Results: Thir ty-nine patients were entered onto the study. Three patients refused t reatment; therefore, 36 patients were eligible for further evaluation. Median follow-up was 36.9 months from treatment end. All patients had elevated initial PSA levels, and 18 patients had PSAs of > 20 ng/ml. Tumor classification was T-2, 12 patients (33.3%); T-3, 22 patients (6 1.1%); and T-4, 2 patients (5.6%). Complete clinical response, defined as PSA < 4 ng/ml and complete clinical disappearance, was attained in 17.9% of (5/28 pts) with information at 90 days and 56% of patients b y 12 months following treatment, Relapse-free survival was 13% at 3 ye ars with PSA < 4 ng/ml. There mere no Grade 4 or 5 toxicities, either acute (during treatment) or in follow-up. Conclusions: Results of this trial regarding PSA response and clinical disappearance of disease ar e similar to historical controls and do not warrant further investigat ion of etanidazole as was done in this trial. Drug toxicity that, in t he past, has been unacceptably high with other hypoxic cell sensitizer s does not appear to be a significant problem with this drug. Copyrigh t (C) 1996 by Elsevier Science Inc.