Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426)

Cancer. 2008 Jun;112(11):2393-400. doi: 10.1002/cncr.23473.

Abstract

Background: Antiandrogen withdrawal is a potential therapeutic maneuver for patients with progressive prostate cancer. This study was designed to examine antiandrogen withdrawal effects within the context of a large multi-institutional prospective trial.

Methods: Eligibility criteria included progressive prostate adenocarcinoma despite combined androgen blockade. Eligible patients received prior initial treatment with an antiandrogen plus orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist. Patients were stratified according to type of antiandrogen, type of progression (prostate-specific antigen [PSA] or radiographic), presence or absence of metastatic disease, and prior LHRH agonist versus surgical castration.

Results: A total of 210 eligible and evaluable patients had a median follow-up of 5.0 years; 64% of patients previously received flutamide, 32% bicalutamide, and 3% nilutamide. Of the 210 patients, 21% of patients had confirmed PSA decreases of >or=50% (95% CI, 16% to 27%). No radiographic responses were recorded. Median progression-free survival (PFS) was 3 months (95% CI, 2 months to 4 months); however, 19% had 12-month or greater progression-free intervals. Median overall survival (OS) after antiandrogen withdrawal was 22 months (20 and 40 months for those with and without radiographic evidence of metastatic disease, respectively). Multivariate analyses indicated that longer duration of antiandrogen use, lower PSA at baseline, and PSA-only progression at study entry were associated with both longer PFS and OS. Longer antiandrogen use was the only significant predictor of PSA response.

Conclusions: These data indicate a relatively modest rate of PSA response in patients who were undergoing antiandrogen withdrawal; however, PFS can be relatively prolonged (>or=1 year) in approximately 19% of patients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / secondary
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use*
  • Anilides / therapeutic use
  • Bone Neoplasms / blood*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Disease-Free Survival
  • Flutamide / therapeutic use
  • Gonadotropin-Releasing Hormone / administration & dosage
  • Humans
  • Imidazolidines / therapeutic use
  • Male
  • Middle Aged
  • Nitriles / therapeutic use
  • Orchiectomy*
  • Prospective Studies
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Substance Withdrawal Syndrome / blood*
  • Substance Withdrawal Syndrome / etiology
  • Survival Rate
  • Tosyl Compounds / therapeutic use

Substances

  • Androgen Antagonists
  • Anilides
  • Imidazolidines
  • Nitriles
  • Tosyl Compounds
  • Gonadotropin-Releasing Hormone
  • nilutamide
  • Flutamide
  • bicalutamide
  • Prostate-Specific Antigen

Grant support