Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: The final results of a European Organization for Research in Cancer Therapy Genitourinary Group trial

Purpose: The outcome of patients with symptomatic metastatic prostate cance r is poor and improved treatment regimens are urgently needed. Theoreticall y, the combination of orchiectomy and chemotherapy could reduce androgen se nsitive and insensitive cells in the prostate. This European Organization f or Research in Cancer Therapy Genitourinary Group randomized, multicenter p hase III trial demonstrates the outcome of orchiectomy alone versus orchiec tomy followed by intravenous mitomycin C. Materials and Methods: A total of 189 patients with metastatic prostate can cer and poor prognostic factors were randomized in this trial by 42 institu tions. Of these patients 184 (97%) were eligible for study, including 90 tr eated with orchiectomy alone (orchiectomy only arm) and 94 treated with orc hiectomy followed by 15 mg./m.(2) mitomycin C in 1 week (combined treatment arm). Mitomycin C was administered every 6 weeks and treatment was continu ed as long as tolerance and patient compliance allowed, and no progression was observed. Objective and subjective criteria for progression were clearl y defined in the protocol. Results: Patient and tumor characteristics were well balanced between the 2 treatment arms. At a median followup of 4.2 years 144 patients had died, i ncluding 112 of prostate cancer. No significant differences for time to ove rall (p = 0.17), subjective (p = 0.25) and objective (p = 0.08) progression were found between the 2 treatment groups. For progression-free survival n o difference was noted (p = 0.07) between the 2, treatment groups but a tre nd in favor of orchiectomy alone was observed for overall survival (p = 0.0 4). Milomycin C induced considerable hematological, gastrointestinal, renal and pulmonary toxicity leading to discontinuation in 31% of patients with pulmonary toxicity and 7% with renal deterioration. In addition, the qualit y of life evaluation revealed significant reduction in the combined treatme nt arm. Conclusions: Based on the results of this randomized phase III study orchie ctomy plus mitomycin C for metastatic prostate cancer in patients with poor prognostic factors cannot be recommended due to failure of improvement in survival and reduced quality of life parameters.