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Single-Therapy Androgen Suppression in Men with Advanced Prostate Cancer: A Systematic Review and Meta-Analysis

Jerome Seidenfeld, PhD; David J. Samson, BA; Vic Hasselblad, PhD; Naomi Aronson, PhD; Peter C. Albertsen, MD; Charles L. Bennett, MD, PhD; and Timothy J. Wilt, MD, MPH
[+] Article, Author, and Disclosure Information

From the Blue Cross and Blue Shield Association Technology Evaluation Center, Chicago, Illinois; Duke University, Durham, North Carolina; University of Connecticut Health Center, Farmington, Connecticut; Chicago Veterans Affairs Medical Center and Northwestern University, Chicago, Illinois; and the Minneapolis Veterans Affairs Medical Center/VISN 13 Center for Chronic Diseases Outcomes Research, Minneapolis, Minnesota.

Acknowledgment: The authors thank Maxine Gere, MS, and Kathleen Ziegler, PharmD, for editorial assistance.

Grant Support: This work was developed under contract with the Agency for Healthcare Research and Quality (AHRQ contract number 290-97-0015). The Blue Cross and Blue Shield Association Technology Evaluation Center is an Evidence-based Practice Center of the AHRQ.

Requests for Single Reprints: Jerome Seidenfeld, PhD, Blue Cross and Blue Shield Association, 225 North Michigan Avenue, Chicago, IL 60601-7680; e-mail, Jerome.Seidenfeld@bcbsa.com.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints@mail.acponline.org.

Current Author Addresses: Drs. Seidenfeld and Aronson: Blue Cross and Blue Shield Association, 225 North Michigan Avenue, Chicago, IL 60601-7680.

Mr. Samson: Blue Cross and Blue Shield Association, 1310 G Street, NW, Washington, DC 20005.

Dr. Hasselblad: Duke Clinical Research Institute, Terrace Level, 2400 Pratt, Room 0311, Durham, NC 27705.

Dr. Albertsen: University of Connecticut Health Center, Division of Urology, 263 Farmington, Farmington, CT 06030-3955.

Dr. Bennett: Veterans Affairs Chicago Health Care Systems, Medical Science Building, 400 East Ontario, Suite 205, Chicago, IL 60611.

Dr. Wilt: Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417.

Ann Intern Med. 2000;132(7):566-577. doi:10.7326/0003-4819-132-7-200004040-00009
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Purpose: To compare luteinizing hormone-releasing hormone (LHRH) agonists with orchiectomy or diethylstilbestrol, and to compare antiandrogens with any of these three alternatives.

Data Sources: A search of the MEDLINE, Cancerlit, EMBASE, and Cochrane Library databases from 1966 to March 1998 and Current Contents to 24 August 1998 for articles comparing the outcomes of the specified treatments. The search was limited to studies on prostatic neoplasms in humans. Total yield was 1477 studies.

Study Selection: Reports of efficacy outcomes were limited to randomized, controlled trials. Twenty-four trials involving more than 6600 patients, phase II studies that reported on withdrawals from therapy (the most reliable indicator of adverse effects), and all studies reporting on quality of life were abstracted.

Data Extraction: Two independent reviewers abstracted each article by following a prospectively designed protocol. The meta-analysis combined data on 2-year overall survival by using a random-effects model and reported results as a hazard ratio relative to orchiectomy.

Data Synthesis: Ten trials of LHRH agonists involving 1908 patients reported no significant difference in overall survival. The hazard ratio showed LHRH agonists to be essentially equivalent to orchiectomy (hazard ratio, 1.262 [95% CI, 0.915 to 1.386]). There was no evidence of difference in overall survival among the LHRH agonists, although CIs were wider for leuprolide (hazard ratio, 1.0994 [CI, 0.207 to 5.835]) and buserelin (hazard ratio, 1.1315 [CI, 0.533 to 2.404]) than for goserelin (hazard ratio, 1.1172 [CI, 0.898 to 1.390]). Evidence from 8 trials involving 2717 patients suggests that nonsteroidal antiandrogens were associated with lower overall survival. The CI for the hazard ratio approached statistical significance (hazard ratio, 1.2158 [CI, 0.988 to 1.496]). Treatment withdrawals were less frequent with LHRH agonists (0% to 4%) than with nonsteroidal antiandrogens (4% to 10%).

Conclusions: Survival after therapy with an LHRH agonist was equivalent to that after orchiectomy. No evidence shows a difference in effectiveness among the LHRH agonists. Survival rates may be somewhat lower if a nonsteroidal antiandrogen is used as monotherapy.


Grahic Jump Location
Figure 2.
Sensitivity analyses for drug categories.center markserror bars

Point estimates for hazard ratios ( ) and 95% CIs ( ) relative to orchiectomy for data on survival after 2 years of treatment. Data on each drug category are pooled for all studies. Also shown are similar pooled analyses limited to studies that excluded patients without extranodal metastases (stage D2 disease) or double-blind studies that reported intention-to-treat analysis (high-quality studies). DES = diethylstilbestrol; LHRHa = luteinizing hormone-releasing hormone agonists; NSAA = nonsteroidal antiandrogen. Numbers in parentheses are pooled numbers of studies and patients, respectively.

Grahic Jump Location
Grahic Jump Location
Figure 1.
Meta-analysis of survival at 2 years.center markserror bars

Point estimates for hazard ratios ( ) and 95% CIs ( ) relative to orchiectomy for data on survival after 2 years of treatment. Data on each monotherapy are pooled for all studies. DES = diethylstilbestrol; LHRHa = luteinizing hormone-releasing hormone agonist; NSAA = nonsteroidal antiandrogen. Numbers in parentheses are pooled numbers of studies and patients, respectively.

Grahic Jump Location




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