Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years

BJU Int. 2010 Apr;105(8):1074-81. doi: 10.1111/j.1464-410X.2010.09319.x.

Abstract

Objective: To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.

Patients and methods: In all, 8113 patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) were enrolled in three complementary, double-blind, placebo-controlled trials. Patients were randomized to receive standard care plus either oral bicalutamide 150 mg once-daily or oral placebo. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collated from individual trials and evaluated in a combined analysis.

Results: Overall, at a median follow-up of 9.7 years, bicalutamide significantly improved PFS (hazard ratio 0.85, 95% confidence interval 0.79-0.91; P= 0.001). Compared with placebo there was no difference in OS (hazard ratio 1.01, P= 0.77). Patients who derived benefit from bicalutamide in terms of PFS were those with locally advanced disease, with OS significantly favouring bicalutamide in patients with locally advanced disease undergoing radiotherapy (P= 0.031). Patients with localized disease showed no clinically or statistically significant improvements in PFS; there was a survival trend in favour of placebo in patients with localized disease undergoing watchful waiting (P= 0.054). The overall tolerability of bicalutamide was consistent with previous analyses, with breast pain (73.7%) and gynaecomastia (68.8%) the most frequently reported adverse events in patients randomized to bicalutamide.

Conclusions: Bicalutamide 150 mg, either as monotherapy or adjuvant to standard care, improved PFS in patients with locally advanced prostate cancer, but not in patients with localized disease. A pre-planned subset analysis showed a benefit for OS in patients with locally advanced disease undergoing radiotherapy. Bicalutamide 150 mg might represent an alternative for patients with locally advanced prostate cancer considering androgen-deprivation therapy.

Trial registration: ClinicalTrials.gov NCT00657904 NCT00672282 NCT00673205.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Anilides / administration & dosage*
  • Anilides / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Disease-Free Survival
  • Double-Blind Method
  • Drug Administration Schedule
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles / administration & dosage*
  • Nitriles / adverse effects
  • Prostatic Neoplasms / drug therapy*
  • Tosyl Compounds / administration & dosage*
  • Tosyl Compounds / adverse effects

Substances

  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents
  • Nitriles
  • Tosyl Compounds
  • bicalutamide

Associated data

  • ClinicalTrials.gov/NCT00657904
  • ClinicalTrials.gov/NCT00672282
  • ClinicalTrials.gov/NCT00673205