PHASE-II TRIAL OF EXTERNAL-BEAM RADIATION WITH ETANIDAZOLE (SR-2508) FOR THE TREATMENT OF LOCALLY ADVANCED PROSTATE-CANCER

Purpose: To evaluate the efficacy and toxicity of the addition of etan idazole (ETA) to external beam radiation. Methods and Materials: Fifty eight previously untreated patients with locally advanced adenocarcin oma of the prostate were entered on a Phase II trial of etanidazole (E TA) combined with standard external beam radiation therapy. ETA was gi ven concurrently with irradiation. Four patients received less than 25 % of the intended dose of ETA and were ineligible for further analysis . The stage of the remaining patients were T-2c-11, T-3-39, T-4-1, bul ky local recurrence after prostatectomy-1, and T-3, N-1-2. Results: Fo rty-five of 54 patients (83.3%) achieved a clinical complete response (CCR) in the prostate and seminal vesicles as judged by digital rectal exam (DRE). Responses were rapid with a median time to CCR of 3.4 mon ths, range 0-22.8 months. Local control was maintained in 82% of the p atients who achieved a CCR. Fifteen of 32 eligible patients with a nor mal DRE underwent prostate biopsies from 12-20 months after treatment, seven had negative biopsies (46.6%). Distant metastases occurred in 1 8 patients (33.3%). Pretreatment prostatic specific antigen (PSA), Gle ason score, and stage were not associated with treatment outcome in a univariate analysis. Conclusion: While ETA plus radiation was associat ed with a rapid CCR, the overall treatment outcome of these patients a ppeared to be similar to published reports of patients receiving RT al one. The rapid response rate may imply biologic activity of the ETA. I n future trials, it may be reasonable to focus on patients at lower ri sk for the subsequent development of distant disease.