Bilateral orchiectomy with or without flutamide for metastatic prostate cancer

Mario A. Eisenberger, Brent A. Blumenstein, E. David Crawford, Gary Miller, David G. McLeod, Patrick J. Loehrer, George Wilding, Kathy Sears, Daniel J. Culkin, Ian M. Thompson, Anton J. Bueschen, Bruce A. Lowe

Research output: Contribution to journalArticle

716 Citations (Scopus)

Abstract

Background: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. Methods: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. Results: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. Conclusions: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.

Original languageEnglish (US)
Pages (from-to)1036-1042
Number of pages7
JournalNew England Journal of Medicine
Volume339
Issue number15
DOIs
StatePublished - Oct 8 1998
Externally publishedYes

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Flutamide
Orchiectomy
Prostatic Neoplasms
Androgen Antagonists
Placebos
Leuprolide
Survival
Poisons
Castration
Gonadotropin-Releasing Hormone
Androgens
Anemia
Prostate
Diarrhea
Adenocarcinoma
Therapeutics
Confidence Intervals
Neoplasm Metastasis
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Eisenberger, M. A., Blumenstein, B. A., Crawford, E. D., Miller, G., McLeod, D. G., Loehrer, P. J., ... Lowe, B. A. (1998). Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. New England Journal of Medicine, 339(15), 1036-1042. https://doi.org/10.1056/NEJM199810083391504

Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. / Eisenberger, Mario A.; Blumenstein, Brent A.; Crawford, E. David; Miller, Gary; McLeod, David G.; Loehrer, Patrick J.; Wilding, George; Sears, Kathy; Culkin, Daniel J.; Thompson, Ian M.; Bueschen, Anton J.; Lowe, Bruce A.

In: New England Journal of Medicine, Vol. 339, No. 15, 08.10.1998, p. 1036-1042.

Research output: Contribution to journalArticle

Eisenberger, MA, Blumenstein, BA, Crawford, ED, Miller, G, McLeod, DG, Loehrer, PJ, Wilding, G, Sears, K, Culkin, DJ, Thompson, IM, Bueschen, AJ & Lowe, BA 1998, 'Bilateral orchiectomy with or without flutamide for metastatic prostate cancer', New England Journal of Medicine, vol. 339, no. 15, pp. 1036-1042. https://doi.org/10.1056/NEJM199810083391504
Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ et al. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. New England Journal of Medicine. 1998 Oct 8;339(15):1036-1042. https://doi.org/10.1056/NEJM199810083391504
Eisenberger, Mario A. ; Blumenstein, Brent A. ; Crawford, E. David ; Miller, Gary ; McLeod, David G. ; Loehrer, Patrick J. ; Wilding, George ; Sears, Kathy ; Culkin, Daniel J. ; Thompson, Ian M. ; Bueschen, Anton J. ; Lowe, Bruce A. / Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. In: New England Journal of Medicine. 1998 ; Vol. 339, No. 15. pp. 1036-1042.
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abstract = "Background: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. Methods: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. Results: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. Conclusions: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.",
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AU - Blumenstein, Brent A.

AU - Crawford, E. David

AU - Miller, Gary

AU - McLeod, David G.

AU - Loehrer, Patrick J.

AU - Wilding, George

AU - Sears, Kathy

AU - Culkin, Daniel J.

AU - Thompson, Ian M.

AU - Bueschen, Anton J.

AU - Lowe, Bruce A.

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N2 - Background: Combined androgen blockade for the treatment of metastatic prostate cancer consists of an antiandrogen drug plus castration. In a previous trial, we found that adding the antiandrogen flutamide to leuprolide acetate (a synthetic gonadotropin-releasing hormone that results in medical ablation of testicular function) significantly improved survival as compared with that achieved with placebo plus leuprolide acetate. In the current trial, we compared flutamide plus bilateral orchiectomy with placebo plus orchiectomy. Methods: We randomly assigned patients who had never received antiandrogen therapy and who had distant metastases from adenocarcinoma of the prostate to treatment with bilateral orchiectomy and either flutamide or placebo. Patients were stratified according to the extent of disease and according to performance status. Results: Of the 1387 patients who were enrolled in the trial, 700 were randomly assigned to the flutamide group and 687 to the placebo group. Overall the incidence of toxic effects was minimal; the only notable differences between the groups were the greater rates of diarrhea and anemia with flutamide. There was no significant difference between the two groups in overall survival (P=0.14). The estimated risk of death (hazard ratio) for flutamide as compared with placebo was 0.91 (90 percent confidence interval, 0.81 to 1.01). Flutamide was not associated with enhanced benefit in patients with minimal disease. Conclusions: The addition of flutamide to bilateral orchiectomy does not result in a clinically meaningful improvement in survival among patients with metastatic prostate cancer.

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