title: 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.
abstract: OBJECTIVE
  The outcome of patients with symptomatic metastatic prostate cancer is poor and improved treatment regimens are urgently needed. Theoretically, the combination of orchiectomy and chemotherapy could reduce androgen sensitive and insensitive cells in the prostate. This European Organization for Research in Cancer Therapy Genitourinary Group randomized, multicenter phase III trial demonstrates the outcome of orchiectomy alone versus orchiectomy followed by intravenous mitomycin C.
  
  
  METHODS
  A total of 189 patients with metastatic prostate cancer and poor prognostic factors were randomized in this trial by 42 institutions. Of these patients 184 (97%) were eligible for study, including 90 treated with orchiectomy alone (orchiectomy only arm) and 94 treated with orchiectomy followed by 15 mg./m.2 mitomycin C in 1 week (combined treatment arm). Mitomycin C was administered every 6 weeks and treatment was continued as long as tolerance and patient compliance allowed, and no progression was observed. Objective and subjective criteria for progression were clearly 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, including 112 of prostate cancer. No significant differences for time to overall (p = 0.17), subjective (p = 0.25) and objective (p = 0.08) progression were found between the 2 treatment groups. For progression-free survival no difference was noted (p = 0.67) between the 2 treatment groups but a trend in favor of orchiectomy alone was observed for overall survival (p = 0.04). Mitomycin 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 quality of life evaluation revealed significant reduction in the combined treatment arm.
  
  
  CONCLUSIONS
  Based on the results of this randomized phase III study orchiectomy 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.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: de Reijke
authors.forename: F I
authors.initials: FI
authors.lastname: Keuppens
authors.forename: P
authors.initials: P
authors.lastname: Whelan
authors.forename: J
authors.initials: J
authors.lastname: Kliment
authors.forename: M R
authors.initials: MR
authors.lastname: Robinson
authors.forename: L A
authors.initials: LA
authors.lastname: Rea
authors.forename: R J
authors.initials: RJ
authors.lastname: Sylvester
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018450:Disease Progression; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000627:therapeutic use*; D009919:Orchiectomy; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D015996:Survival Rate
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin