Administering Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer 1–6 Days Compared to More than 14 Days after the Start of LHRH Agonist Is Associated with Better Clinical Outcomes Due to Androgen Flare

Abstract

Docetaxel, when given at the beginning of androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (MHSPC), results in significantly longer overall survival than ADT alone. We aimed to investigate if the delivery of the first dose of docetaxel during the testosterone flare associated with LHRH initiation results in better clinical outcomes, as testosterone induces mitosis of prostate cancer cells, and docetaxel specifically targets cells in mitosis. We analyzed data from the CHAARTED trial which randomized MHSPC patients to ADT alone or ADT plus docetaxel. We included only patients treated with LHRH agonist and docetaxel (n = 379). The only cutoff that resulted in differences in treatment outcomes was between patients who started docetaxel 1–6 days (n = 18) compared to more than 14 days from LHRH initiation (n = 297). Actuarial median overall survival was 72 versus 57 months (p = 0.2); progression-free survival was 49 versus 17 months (p = 0.06), and freedom from castrate-resistant prostate cancer was 51 versus 18 months (p = 0.04) for patients who started docetaxel 1–6 days compared to more than 14 days from LHRH initiation, respectively. Administering docetaxel 1–6 days from the initiation of LHRH agonist for patients with MHSPC could be associated with improved clinical outcomes. © 2022 by the authors.