Schweizer Michael T, Gulati Roman, Mostaghel Elahe A, Nelson Peter S, Montgomery R Bruce, Yu Evan Y, Cheng Heather H
Division of Oncology, Department of Medicine, University of Washington, Seattle, WA, 98109, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
Med Oncol. 2016 Jul;33(7):77. doi: 10.1007/s12032-016-0793-1. Epub 2016 Jun 14.
Docetaxel plus androgen deprivation therapy (ADT) offers a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, one trial evaluating docetaxel in mHSPC (GETUG-AFU15) showed unexpected toxicity; raising concerns that docetaxel may carry increased toxicity when used to treat mHSPC compared to metastatic castration-resistant prostate cancer (mCRPC). We conducted a retrospective analysis evaluating differences in toxicity based on the clinical state (i.e., mHSPC vs. mCRPC) that docetaxel was used. Patients initiating docetaxel between 1/1/2014 and 7/15/2015 were included, with the former date chosen to coincide with the press release for the first mHSPC study that showed a survival benefit with early docetaxel; ensuring contemporary docetaxel-treated cohorts. Thirty-nine mCRPC and 22 mHSPC patients were included. Compared to mCRPC, mHSPC patients were younger (median years: 66.3 vs. 71.8, P = 0.007); had better performance status (ECOG 0-1: 100 vs. 62 %, P < 0.0001); and used opiates less frequently (29 vs. 66 %, P = 0.04). Neutropenic fevers occurred in 9 and 5 % (P = 0.95) of men with mHSPC and mCRPC, respectively. Other toxicities also occurred at similar rates between cohorts. The incidence of any toxic event was 73 and 67 % (P = 0.84) for men with mHSPC and mCRPC, respectively. Within the mHSPC cohort, neutropenic fevers occurred at a similar rate regardless of the time interval between initiating ADT and the start of docetaxel. We did not observe a significant difference in toxicity between mHSPC and mCRPC patients receiving docetaxel. However, the small sample size and retrospective nature of this study limit our ability to draw definitive conclusions.
多西他赛联合雄激素剥夺疗法（ADT）可使转移性激素敏感性前列腺癌（mHSPC）患者的生存期延长。然而，一项评估多西他赛用于mHSPC的试验（GETUG-AFU15）显示出意外的毒性；这引发了人们的担忧，即与转移性去势抵抗性前列腺癌（mCRPC）相比，多西他赛用于治疗mHSPC时可能具有更高的毒性。我们进行了一项回顾性分析，以评估基于多西他赛使用时的临床状态（即mHSPC与mCRPC）的毒性差异。纳入了2014年1月1日至2015年7月15日期间开始使用多西他赛的患者，选择前者日期是为了与首次显示早期多西他赛具有生存获益的mHSPC研究的新闻稿发布时间一致；确保是当代接受多西他赛治疗的队列。纳入了39例mCRPC患者和22例mHSPC患者。与mCRPC患者相比，mHSPC患者更年轻（中位年龄：66.3岁对71.8岁，P = 0.007）；体能状态更好（东部肿瘤协作组[ECOG] 0-1级：100%对62%，P < 0.0001）；使用阿片类药物的频率更低（29%对66%，P = 0.04）。mHSPC和mCRPC男性患者中分别有9%和5%发生中性粒细胞减少性发热（P = 0.95）。其他毒性在各队列中的发生率也相似。mHSPC和mCRPC男性患者中任何毒性事件的发生率分别为73%和67%（P = 0.84）。在mHSPC队列中，无论开始ADT与开始多西他赛之间的时间间隔如何，中性粒细胞减少性发热的发生率相似。我们未观察到接受多西他赛治疗的mHSPC和mCRPC患者在毒性方面存在显著差异。然而，本研究的样本量小且具有回顾性，限制了我们得出确定性结论的能力。
