Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

BACKGROUND: Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.

METHODS: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of the body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.

RESULTS: A total of 790 patients (median age, 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infections with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.

CONCLUSIONS: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.)

The New England Journal of Medicine. 2015 August 5 [Epub ahead of print]

Christopher J. Sweeney, MB, BS,^1,3 Yu-Hui Chen, MS, MPH,² Michael Carducci, MD,⁴ Glenn Liu, MD,⁵ David F. Jarrard, MD,^5,6 Mario Eisenberger, MD,⁴ Yu-Ning Wong, MD, MSCE,⁷ Noah Hahn, MD,⁸ Manish Kohli, MD,⁹ Matthew M. Cooney, MD,¹⁰ Robert Dreicer, MD,¹² Nicholas J. Vogelzang, MD,¹³ Joel Picus, MD,¹⁴ Daniel Shevrin, MD,¹⁵ Maha Hussain, MB, ChB,¹⁶ Jorge A. Garcia, MD,¹¹ and Robert S. DiPaola, MD¹⁷
1. Department of Medicine, Dana–Farber Cancer Institute, Boston, Massachusetts
2. Department of Biostatistics and Computational Biology, Dana–Farber Cancer Institute, Boston, Massachusetts
3. Harvard Medical School, Boston, Massachusetts
4. Johns Hopkins University, Baltimore, Maryland
5. University of Wisconsin Carbone Cancer Center, Madison, Wisconsin
6. University Of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
7. Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
8. Indiana University Melvin and Bren Simon Cancer Center, Indianapolis
9. Mayo Clinic, Rochester, Minnesota
10. University Hospitals Case Medical Center, Seidman Cancer Center, Cleveland, Ohio
11. Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio
12. University of Virginia Cancer Center, Charlottesville, Virginia
13. Comprehensive Cancer Centers of Nevada, Las Vegas, Nevada
14. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri
15. NorthShore University HealthSystem, Evanston, Illinois
16. University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan
17. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey

N Engl J Med 2015; 373:737-746; DOI: 10.1056/NEJMoa1503747

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