The timing of docetaxel initiation in metastatic castrate-sensitive prostate cancer and the rate of chemotherapy-induced toxicity
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Docetaxel pharmacokinetics are affected by androgen deprivation therapy (ADT), which is attributed to changes in liver metabolism induced by castration. In this retrospective analysis, we assessed whether initiating docetaxel treatment in close proximity to the start of ADT therapy for metastatic castrate-sensitive prostate cancer (mCSPC) is associated with more treatment-related toxicity. We identified all patients with mCSPC treated at The Ottawa Hospital that received docetaxel chemotherapy between June 2014 and September 2017. For each patient, we calculated the time to chemotherapy (TTC) interval between the start of ADT and the first cycle of docetaxel. We checked for an association between TTC and febrile neutropenia (FN), toxicity-induced dose reduction, toxicity-induced treatment delay, and toxicity-induced treatment discontinuation. Eighty-three patients were identified. The median TTC was 67 days (range 3–189). Twenty-three patients (27.7%) experienced FN. Docetaxel toxicity resulted in 8 patients (9.6%) having their treatment delayed, 30 patients (36.1%) having their dose reduced and 18 (21.6%) having their treatment discontinued before completing the scheduled 6 cycles. No correlation was found between the TTC and FN (P = 0.99), docetaxel dose reduction (P = 0.95), treatment delay (P = 0.06), and treatment discontinuation (P = 0.88). The timing of docetaxel treatment initiation in relation to ADT initiation in patients with mCSPC did not affect the rate of treatment-related toxicity. Therefore, there is no indication for upfront chemotherapy delay from start of ADT unless clinical factors warrant a delay in starting chemotherapy. A higher than expected FN rate was identified, and primary prophylaxis should be considered.
KeywordsProstate cancer Castrate-sensitive Docetaxel Toxicity
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
CC declared: Honorarium—Janssen; Advisory boards—Roche, Ipsen, Pfizer, Eisai, Merk, EMD Serono, Bayer, BMS, AstraZeneca, Janssen; Travel support—Sanofi, Amgen, Pfizer; Research funding – Eisai. DB declared: Advisory/honorarium—BMS, Pfizer, AbbVie, and AstraZenaca. NMR declared: Honoraria—Astellas, Novartis, Janssen, Roche, Pfizer, AstraZeneca. IK, KK, MO, ES declare no conflict of interest associated with this publication.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
For this retrospective study formal consent was not required by the Ottawa Health Science Network Research Ethics Board.
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