Combined androgen blockade with bicalutamide for advanced prostate cancer

Long-term follow-up of a phase 3, double-blind, randomized study for survival

Hideyuki Akaza, Shiro Hinotsu, Michiyuki Usami, Yoichi Arai, Hiroshi Kanetake, Seiji Naito, Yoshihiko Hirao

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

BACKGROUND: A previously reported, double-blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone-releasing hormone agonist (LHRH-A) plus bicalutamide 80 mg versus LHRH-A plus bicalutamide-matching placebo (LHRH-A monotherapy). The analysis at a median follow-up of 2.4 years indicated that CAB significantly (P <.001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long-term follow-up (median, 5.2 years) were analyzed. METHODS: All deaths irrespective of cause and all prostate cancer-specific deaths were recorded. The data were analyzed using Cox regression analysis and the log-rank test. RESULTS: At a median follow-up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH-A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95% confidence interval, 0.60-0.99; P = .0498; log-rank test: P = .0425). The difference in cause-specific survival between the 2 groups was not significant. The achievement of a prostate-specific antigen (PSA) nadir concentration ≤1 ng/mL was a prognostic factor for improved survival. More patients attained PSA nadir concentrations ≤1 ng/mL with CAB compared with patients who received LHRH-A monotherapy (81.4% vs 33.7%; P <.001). CONCLUSIONS: CAB with bicalutamide 80 mg offered a significant overall survival benefit compared with LHRH-A monotherapy without reducing tolerability in patients with locally advanced or metastatic prostate cancer.

Original languageEnglish
Pages (from-to)3437-3445
Number of pages9
JournalCancer
Volume115
Issue number15
DOIs
Publication statusPublished - Aug 1 2009
Externally publishedYes

Fingerprint

Double-Blind Method
Gonadotropin-Releasing Hormone
Androgens
Prostatic Neoplasms
Survival
Prostate-Specific Antigen
Regression Analysis
Treatment Failure
bicalutamide
Cause of Death
Placebos
Confidence Intervals

Keywords

  • Bicalutamide
  • Clinical trial
  • Combined androgen blockade
  • Deferred combined androgen blockade
  • Immediate combined androgen blockade
  • Luteinizing hormone-releasing hormone agonist
  • Prostate cancer
  • Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Combined androgen blockade with bicalutamide for advanced prostate cancer : Long-term follow-up of a phase 3, double-blind, randomized study for survival. / Akaza, Hideyuki; Hinotsu, Shiro; Usami, Michiyuki; Arai, Yoichi; Kanetake, Hiroshi; Naito, Seiji; Hirao, Yoshihiko.

In: Cancer, Vol. 115, No. 15, 01.08.2009, p. 3437-3445.

Research output: Contribution to journalArticle

Akaza, Hideyuki ; Hinotsu, Shiro ; Usami, Michiyuki ; Arai, Yoichi ; Kanetake, Hiroshi ; Naito, Seiji ; Hirao, Yoshihiko. / Combined androgen blockade with bicalutamide for advanced prostate cancer : Long-term follow-up of a phase 3, double-blind, randomized study for survival. In: Cancer. 2009 ; Vol. 115, No. 15. pp. 3437-3445.
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abstract = "BACKGROUND: A previously reported, double-blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone-releasing hormone agonist (LHRH-A) plus bicalutamide 80 mg versus LHRH-A plus bicalutamide-matching placebo (LHRH-A monotherapy). The analysis at a median follow-up of 2.4 years indicated that CAB significantly (P <.001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long-term follow-up (median, 5.2 years) were analyzed. METHODS: All deaths irrespective of cause and all prostate cancer-specific deaths were recorded. The data were analyzed using Cox regression analysis and the log-rank test. RESULTS: At a median follow-up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH-A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95{\%} confidence interval, 0.60-0.99; P = .0498; log-rank test: P = .0425). The difference in cause-specific survival between the 2 groups was not significant. The achievement of a prostate-specific antigen (PSA) nadir concentration ≤1 ng/mL was a prognostic factor for improved survival. More patients attained PSA nadir concentrations ≤1 ng/mL with CAB compared with patients who received LHRH-A monotherapy (81.4{\%} vs 33.7{\%}; P <.001). CONCLUSIONS: CAB with bicalutamide 80 mg offered a significant overall survival benefit compared with LHRH-A monotherapy without reducing tolerability in patients with locally advanced or metastatic prostate cancer.",
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AU - Usami, Michiyuki

AU - Arai, Yoichi

AU - Kanetake, Hiroshi

AU - Naito, Seiji

AU - Hirao, Yoshihiko

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AB - BACKGROUND: A previously reported, double-blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone-releasing hormone agonist (LHRH-A) plus bicalutamide 80 mg versus LHRH-A plus bicalutamide-matching placebo (LHRH-A monotherapy). The analysis at a median follow-up of 2.4 years indicated that CAB significantly (P <.001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long-term follow-up (median, 5.2 years) were analyzed. METHODS: All deaths irrespective of cause and all prostate cancer-specific deaths were recorded. The data were analyzed using Cox regression analysis and the log-rank test. RESULTS: At a median follow-up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH-A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95% confidence interval, 0.60-0.99; P = .0498; log-rank test: P = .0425). The difference in cause-specific survival between the 2 groups was not significant. The achievement of a prostate-specific antigen (PSA) nadir concentration ≤1 ng/mL was a prognostic factor for improved survival. More patients attained PSA nadir concentrations ≤1 ng/mL with CAB compared with patients who received LHRH-A monotherapy (81.4% vs 33.7%; P <.001). CONCLUSIONS: CAB with bicalutamide 80 mg offered a significant overall survival benefit compared with LHRH-A monotherapy without reducing tolerability in patients with locally advanced or metastatic prostate cancer.

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KW - Survival

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