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Bilateral orchiectomy with or without flutamide for metastatic prostate cancer.
Open accessAbstract
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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“The first generation of true antiandrogen molecules used in the clinic, including bicalutamide (Casodex) and flutamide, aimed at inhibiting AR transcriptional activity by specifically targeting ligand binding to the AR (8,9).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [9]
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Metadata
- Authors
- Eisenberger, M. A., Blumenstein, B. A., Crawford, E. D., Miller, G., McLeod, D. G., Loehrer, P. J., Wilding, G., Sears, K., Culkin, D. J., Thompson, I. M., Bueschen, A. J., & Lowe, B. A.
- Affiliations
- Johns Hopkins Hospital (US)
- SWOG Cancer Research Network (US)
- University of Colorado Denver (US)
- Walter Reed National Military Medical Center (US)
- University of Wisconsin–Madison (US)
- University of Oklahoma Health Sciences Center (US)
- University of Alabama at Birmingham (US)
- Oregon Health & Science University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-10-08
- Volume
- 339
- Issue
- 15
- Pages
- 1036-1042
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2003985632
- Cited by
- 859
- References
- 25
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 20 · 2021: 15 · 2020: 21 · 2019: 26 · 2018: 25 · 2017: 23 · 2016: 34 · 2015: 52 · 2014: 49 · 2013: 51 · 2012: 37
- FWCI
- 37.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2u10ca038926-25)
- National Cancer Institute (CA-32102, CA 42777, U10CA032102, U10CA042777, CA 38926)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- metastatic prostate cancer, bilateral orchiectomy, flutamide, combined androgen blockade, leuprolide, antiandrogen therapy, overall survival, adverse effects, anemia, diarrhea
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Androgen Antagonists, Bone Neoplasms, Combined Modality Therapy, Double-Blind Method, Flutamide, Humans, Male, Middle Aged, Orchiectomy, Prostatic Neoplasms, Soft Tissue Neoplasms, Survival Analysis, Prostate-Specific Antigen
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