1. Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial.
- Author
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D'Amico AV, Xie W, McMahon E, Loffredo M, Medeiros S, Joseph D, Denham J, Kumar P, Bubley G, Sullivan M, Hellwig R, Carlos Vera J, Freter R, Jeffrey Baker W, Wong JY, Renshaw AA, and Kantoff PW
- Subjects
- Androgen Antagonists adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Australia, Docetaxel adverse effects, Humans, Kallikreins blood, Male, Neoplasm Staging, Neoplasms, Radiation-Induced etiology, Neoplasms, Radiation-Induced prevention & control, New Zealand, Prospective Studies, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Prostatic Neoplasms mortality, Prostatic Neoplasms pathology, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, United States, Androgen Antagonists therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoradiotherapy adverse effects, Chemoradiotherapy mortality, Docetaxel therapeutic use, Prostatic Neoplasms therapy
- Abstract
Purpose: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist., Methods: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m
2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors., Results: After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL., Conclusion: Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality., Competing Interests: Molly SullivanEmployment: Moderna Therapeutics, Elektrofi Jeffrey Y. WongResearch Funding: Accuray, Varian Medical Systems Philip W. KantoffLeadership: Context Therapeutics, XLinkStock and Other Ownership Interests: Placon, Druggablity Technologies, Context Therapeutics, Seer, Cogent Biosciences, Mirati Therapeutics, PrognomIQ, SynDevRx, XLinkConsulting or Advisory Role: Janssen, Merck, OncoCellMDX, Genentech/Roche, Tarveda Therapeutics, Druggablity Technologies, Progenity, Seer, Anji, Candel Therapeutics, Context Therapeutics, PrognomIQ, SynDevRx, Veru, XLinkPatents, Royalties, Other Intellectual Property: Method for Predicting the Risk of Prostate Cancer Morbidity and Mortality, Predicting and Treating Prostate Cancer, Methods for Predicting Likelihood of Responding to Treatment, Chromosome Copy Number Gain as a Biomarker of Urothelial Carcinoma Lethality, Drug Combinations to Treat Cancer, Somatic ERCC2 Mutations Correlate With Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma (Patent), UpToDate Royalties, Wolters Kluwer Royalties, Methods and Kits for Determining Sensitivity to Cancer Treatment, Composition and Methods for Screening and Diagnosis of Prostate CancerOther Relationship: BayerOpen Payments Link: https://openpaymentsdata.cms.gov/physician/55315/summaryNo other potential conflicts of interest were reported.- Published
- 2021
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