The Ottawa Hospital Cancer Centre and University of Ottawa, Ottawa, ON, Canada.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Cancer Chemother Pharmacol. 2020 May;85(5):863-868. doi: 10.1007/s00280-020-04063-7. Epub 2020 Apr 2.
Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS).
All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA).
Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09-1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61-0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02-1.36, P = 0.026).
Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.
几项研究评估了转移性去势抵抗性前列腺癌（mCRPC）患者多西他赛剂量强度（DI）与疗效的相关性，但结论相互矛盾。在这项回顾性分析中，我们将评估转移性去势敏感前列腺癌（mCSPC）患者使用的多西他赛 DI 是否与总生存期（OS）相关。
在渥太华医院癌症中心接受多西他赛化疗的所有 mCSPC 患者，均在 2014 年 6 月至 2017 年 9 月间接受治疗。使用单变量和多变量 Cox 模型，通过调整年龄、Gleason 评分、疾病负担、内脏转移、初发转移和基线前列腺特异性抗原（PSA），评估相对剂量强度（RDI）与 OS 的相关性。
81 例患者纳入分析。只有 35 例（43%）患者能够完成至少 90%计划治疗的多西他赛治疗，RDI 为 100%。单变量分析显示，较高的 RDI 和接受的多西他赛周期数与更长的 OS 相关。RDI 每降低 10%，死亡风险增加 23%（HR 1.23，95%CI 1.09-1.4，P=0.001）。每增加一个周期（最多六个），死亡风险降低 27%（HR 0.73，95%CI 0.61-0.88，P=0.001）。多变量分析显示，降低的 RDI 是唯一与 OS 显著相关的预测因素（HR 1.18，95%CI 1.02-1.36，P=0.026）。
我们的研究表明，在 mCSPC 中，降低的多西他赛 RDI 与较短的生存期相关。应避免不必要的剂量减少、治疗延迟和早期停药。为维持标准 DI，可考虑使用粒细胞集落刺激因子。
