Anne M Horgan1, Bostjan Seruga2, Greg R Pond3, Shabbir M Alibhai4, Eitan Amir4, Ronald De Wit5, Mario A Eisenberger6, Ian F Tannock4. 1. Department of Medical Oncology, Princess Margaret Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada; Department of Medical Oncology, Waterford Regional Hospital, Waterford, Ireland. Electronic address: annem.horgan@hse.ie. 2. Sector of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia. 3. Department of Oncology and Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada. 4. Department of Medical Oncology, Princess Margaret Hospital, University Health Network and the University of Toronto, Toronto, Ontario, Canada. 5. Department of Medical Oncology, Erasmus University Medical Center and Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. 6. Johns Hopkins University-School of Medicine, Oncology Center, Baltimore, United States.
Abstract
OBJECTIVE: Prostate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population. MATERIALS AND METHODS: Two subgroup analyses of TAX 327 were conducted. Among patients receiving DPq3w, tolerability and efficacy were compared between three age groups: <65, 65-74 and ≥75 years. For men ≥75 years, these outcomes were compared between DPq3w, DPq1w, and mitoxantrone (MP) arms. Tolerability outcomes included dose delivery, grade 3/4 adverse events and quality of life. Efficacy outcomes included overall survival and tumor response. RESULTS: Of 1006 men with metastatic castrate-resistant prostate cancer (mCRPC) in the trial, 335 received DPq3w. Among these, 20% were age ≥75 years. For DPq3w, there were non-significant associations of worse tolerability and efficacy with advancing age. Twenty-eight percent of men age ≥75 years had an objective pain response, compared to 38% and 34% of patients 65-74 and <65 years, respectively. There were no significant differences in prostate-specific antigen (PSA) response (43-48%, p = 0.74) or measurable tumor response (7-17%, p = 0.30) according to age. Among men ≥75 years, DPq3w resulted in more dose reductions than DPq1w (22% versus 8%, p = 0.007), but tolerability was otherwise comparable. Both were associated with more favorable efficacy than mitoxantrone. CONCLUSIONS: Tolerability and efficacy of DPq3w appear less favorable with advancing age. Compared to DPq1w, DPq3w is associated with better survival outcomes, but similar tolerability, and remains the standard first-line chemotherapy option in mCRPC. Toxicity is substantial, therefore careful patient selection, close monitoring and early management of toxicities is advised.
OBJECTIVE:Prostate cancer is a disease of older men. Weekly docetaxel (DPq1w) is often favored over the standard three-weekly regimen (DPq3w) due to concerns about safety and tolerability in this population. MATERIALS AND METHODS: Two subgroup analyses of TAX 327 were conducted. Among patients receiving DPq3w, tolerability and efficacy were compared between three age groups: <65, 65-74 and ≥75 years. For men ≥75 years, these outcomes were compared between DPq3w, DPq1w, and mitoxantrone (MP) arms. Tolerability outcomes included dose delivery, grade 3/4 adverse events and quality of life. Efficacy outcomes included overall survival and tumor response. RESULTS: Of 1006 men with metastatic castrate-resistant prostate cancer (mCRPC) in the trial, 335 received DPq3w. Among these, 20% were age ≥75 years. For DPq3w, there were non-significant associations of worse tolerability and efficacy with advancing age. Twenty-eight percent of men age ≥75 years had an objective pain response, compared to 38% and 34% of patients 65-74 and <65 years, respectively. There were no significant differences in prostate-specific antigen (PSA) response (43-48%, p = 0.74) or measurable tumor response (7-17%, p = 0.30) according to age. Among men ≥75 years, DPq3w resulted in more dose reductions than DPq1w (22% versus 8%, p = 0.007), but tolerability was otherwise comparable. Both were associated with more favorable efficacy than mitoxantrone. CONCLUSIONS: Tolerability and efficacy of DPq3w appear less favorable with advancing age. Compared to DPq1w, DPq3w is associated with better survival outcomes, but similar tolerability, and remains the standard first-line chemotherapy option in mCRPC. Toxicity is substantial, therefore careful patient selection, close monitoring and early management of toxicities is advised.
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