Maximal androgen blockade for patients with metastatic prostate cancer

Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy

Paul Schellhammer, Roohollah Sharifi, Norman Block, Mark Soloway, Peter Venner, Anthony Patterson, Michael Sarosdy, Nicholas Vogelzang, Julie Jones, Geert Kolvenbag

Research output: Contribution to journalArticle

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Abstract

Objectives. To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. Methods. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 × 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). Results. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (<1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (<1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P<0.001). Conclusions. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Original languageEnglish (US)
Pages (from-to)54-60
Number of pages7
JournalUrology
Volume47
Issue number1 SUPPL. 1
StatePublished - Dec 1 1996

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Flutamide
Gonadotropin-Releasing Hormone
Androgens
Prostatic Neoplasms
Therapeutics
Treatment Failure
Androgen Antagonists
bicalutamide
Survival
Goserelin
Confidence Intervals
Leuprolide

All Science Journal Classification (ASJC) codes

  • Urology

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Maximal androgen blockade for patients with metastatic prostate cancer : Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. / Schellhammer, Paul; Sharifi, Roohollah; Block, Norman; Soloway, Mark; Venner, Peter; Patterson, Anthony; Sarosdy, Michael; Vogelzang, Nicholas; Jones, Julie; Kolvenbag, Geert.

In: Urology, Vol. 47, No. 1 SUPPL. 1, 01.12.1996, p. 54-60.

Research output: Contribution to journalArticle

Schellhammer, P, Sharifi, R, Block, N, Soloway, M, Venner, P, Patterson, A, Sarosdy, M, Vogelzang, N, Jones, J & Kolvenbag, G 1996, 'Maximal androgen blockade for patients with metastatic prostate cancer: Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy', Urology, vol. 47, no. 1 SUPPL. 1, pp. 54-60.
Schellhammer, Paul ; Sharifi, Roohollah ; Block, Norman ; Soloway, Mark ; Venner, Peter ; Patterson, Anthony ; Sarosdy, Michael ; Vogelzang, Nicholas ; Jones, Julie ; Kolvenbag, Geert. / Maximal androgen blockade for patients with metastatic prostate cancer : Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy. In: Urology. 1996 ; Vol. 47, No. 1 SUPPL. 1. pp. 54-60.
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title = "Maximal androgen blockade for patients with metastatic prostate cancer: Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy",
abstract = "Objectives. To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. Methods. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 × 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). Results. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68{\%} of patients in the bicalutamide plus LHRH-A group, compared with 72{\%} of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95{\%} confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95{\%} confidence limit for survival was 1.00, meeting the definition for equivalence (<1.25). With longer follow-up, overall mortality was 34{\%}, with equivalent survival between groups: 32{\%} of patients in the bicalutamide plus LHRH-A group died, compared with 35{\%} in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95{\%} CI, 0.69-1.11; P = 0.29). The upper one-sided 95{\%} confidence limit for survival was 1.07, meeting the definition for equivalence (<1.25). Diarrhea occurred in 24{\%} of patients in the flutamide plus LHRH-A group compared with 10{\%} of patients in the bicalutamide plus LHRH-A group (P<0.001). Conclusions. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.",
author = "Paul Schellhammer and Roohollah Sharifi and Norman Block and Mark Soloway and Peter Venner and Anthony Patterson and Michael Sarosdy and Nicholas Vogelzang and Julie Jones and Geert Kolvenbag",
year = "1996",
month = "12",
day = "1",
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TY - JOUR

T1 - Maximal androgen blockade for patients with metastatic prostate cancer

T2 - Outcome of a controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy

AU - Schellhammer, Paul

AU - Sharifi, Roohollah

AU - Block, Norman

AU - Soloway, Mark

AU - Venner, Peter

AU - Patterson, Anthony

AU - Sarosdy, Michael

AU - Vogelzang, Nicholas

AU - Jones, Julie

AU - Kolvenbag, Geert

PY - 1996/12/1

Y1 - 1996/12/1

N2 - Objectives. To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. Methods. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 × 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). Results. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (<1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (<1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P<0.001). Conclusions. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

AB - Objectives. To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer. Methods. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 × 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). Results. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (<1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (<1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P<0.001). Conclusions. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

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