Division of Medical Oncology, University of British Columbia, BC Cancer, Vancouver, British Columbia.
Division of Medical Oncology, University of British Columbia, BC Cancer, Victoria, British Columbia.
Prostate. 2019 Feb;79(3):281-287. doi: 10.1002/pros.23733. Epub 2018 Oct 28.
Adding docetaxel to androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) has known efficacy, with an overall survival benefit in Phase III clinical trials. The effectiveness of docetaxel with ADT in the general patient population remains undefined.
We conducted a population-based retrospective review using the British Columbia Provincial Pharmacy Database. To be included, patients had to have castration-sensitive prostate cancer not previously treated (except in the adjuvant setting) and have received at least one cycle of docetaxel, with complete records available for review. Safety and clinical effectiveness were evaluated.
From April 2015 to February 2017, we identified 183 cases; 156 met inclusion criteria. Most patients had high-volume disease (80%). All 6 planned docetaxel cycles were delivered in 126 cases (81%). Dose reductions and delays were required in 39% and 16% of cases. Grade 3-4 adverse events were noted in 40%, with no treatment-related deaths. The rate of febrile neutropenia was 18% and was significantly associated with the presence of high-volume disease (P = 0.038). PSA ≤ 0.2 ng/L was achieved in 27% of patients after 6 months of ADT and maintained in 16% after 12 months. Patients with over 20 bone metastases had worse time to castration resistant prostate cancer (CRPC) and time to treatment for CRPC, and a trend toward worse overall survival. CRPC developed in 41% within 1 year, with a median time to CRPC of 14.4 months. Treatment for CRPC was given in 84 cases, with 90% receiving either abiraterone or enzalutamide in the first-line, with a PSA decline ≥50% occurring in 47%.
The effectiveness of docetaxel with ADT in a general population of patients with mCSPC was associated with poorer outcomes and high rates of toxicity compared to the published studies. Response rates to first-line treatment for mCRPC with abiraterone or enzalutamide appear similar to reported outcomes.
在治疗转移性去势敏感前列腺癌（mCSPC）中，将多西他赛加入雄激素剥夺疗法（ADT）已被证实具有疗效，在 III 期临床试验中具有总生存获益。多西他赛联合 ADT 在一般患者人群中的有效性尚不清楚。
我们使用不列颠哥伦比亚省药房数据库进行了一项基于人群的回顾性研究。纳入标准为患有未经治疗（除辅助治疗外）的去势敏感前列腺癌的患者，且至少接受过一个周期的多西他赛治疗，并有完整的记录可供审查。评估了安全性和临床疗效。
2015 年 4 月至 2017 年 2 月，我们共发现 183 例患者，其中 156 例符合纳入标准。大多数患者存在高肿瘤负荷（80%）。126 例患者（81%）完成了 6 个计划的多西他赛周期。39%和 16%的患者需要减少剂量和延迟治疗。40%的患者出现 3-4 级不良事件，无治疗相关死亡。发热性中性粒细胞减少症的发生率为 18%，与高肿瘤负荷显著相关（P=0.038）。在 ADT 治疗 6 个月后，27%的患者 PSA≤0.2ng/L，12 个月后 16%的患者 PSA 仍维持在该水平。骨转移超过 20 处的患者发生去势抵抗性前列腺癌（CRPC）和治疗 CRPC 的时间更差，总生存时间也有恶化趋势。41%的患者在 1 年内发生 CRPC，中位 CRPC 时间为 14.4 个月。84 例患者接受了 CRPC 的治疗，90%的患者一线治疗采用阿比特龙或恩杂鲁胺，其中 47%的患者 PSA 下降≥50%。
与已发表的研究相比，多西他赛联合 ADT 在 mCSPC 一般人群中的疗效较差，且毒性发生率较高。阿比特龙或恩杂鲁胺治疗 mCRPC 的一线治疗反应率似乎与报告的结果相似。
