Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences

Prostate. 2001 Jun 15;48(1):29-39. doi: 10.1002/pros.1078.

Abstract

Background: The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results.

Methods: The design and results of three trials were examined.

Results: Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration.

Conclusions: Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Anilides / therapeutic use
  • Clinical Trials, Phase III as Topic*
  • Cyproterone Acetate / therapeutic use
  • Factor Analysis, Statistical
  • Flutamide / therapeutic use
  • Gonadotropin-Releasing Hormone / agonists
  • Goserelin / therapeutic use
  • Humans
  • Imidazoles / therapeutic use
  • Imidazolidines*
  • Leuprolide / therapeutic use
  • Male
  • Meta-Analysis as Topic
  • Nitriles
  • Orchiectomy*
  • Prognosis
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / therapy*
  • Research Design
  • Survival Analysis
  • Tosyl Compounds
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Anilides
  • Imidazoles
  • Imidazolidines
  • Nitriles
  • Tosyl Compounds
  • Goserelin
  • Gonadotropin-Releasing Hormone
  • Cyproterone Acetate
  • nilutamide
  • Flutamide
  • bicalutamide
  • Leuprolide