Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Prostate. 2022 Oct;82(14):1322-1330. doi: 10.1002/pros.24406. Epub 2022 Jun 29.
Docetaxel-related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life-threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel-related AE in metastatic prostate cancer (mPCa) patients.
We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration-resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model.
The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10-5.18 and OR: 15.8, 95% CI: 7.23-34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13-4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN.
Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision-making for proper candidate selection of docetaxel treatment.
多西他赛相关的不良反应（AE），如中性粒细胞减少症和发热性中性粒细胞减少症（FN），可能危及生命。先前的体内研究提出了一个假说，即去势状态会影响血液学 AE 的发生率。我们旨在研究去势状态对转移性前列腺癌（mPCa）患者多西他赛相关 AE 发生率的影响。
我们回顾性分析了 265 例接受多西他赛治疗的 mPCa 患者的记录，包括 92 例转移性激素敏感前列腺癌（mHSPC）患者和 173 例转移性去势抵抗性前列腺癌（mCRPC）患者，时间范围为 2015 年 1 月至 2021 年 12 月。采用常见不良事件术语标准（CTCAE）评估 AE。我们分析了 mHSPC 和 mCRPC 之间的差异发生率，并使用逻辑回归模型分析血液学和非血液学 AE 的危险因素。
与 mCRPC 相比，mHSPC 患者接受中性粒细胞减少预防性治疗的比例更高（7.5% vs. 33%，p<0.001）。在未接受预防性治疗的患者中，mCRPC 患者严重中性粒细胞减少症（CTCAE≥3 级）和 FN 的发生率分别为 89%和 16%，而 mHSPC 患者的发生率分别为 81%和 18%。逻辑回归分析显示，年龄≥75 岁和未提供预防性治疗是严重中性粒细胞减少症的独立危险因素（比值比[OR]：2.39，95%置信区间[CI]：1.10-5.18 和 OR：15.8，95% CI：7.23-34.6）。东部肿瘤协作组体能状态（ECOG-PS）≥1 是 FN 的独立危险因素（OR：2.26，95% CI：1.13-4.54）。去势状态（mHSPC 与 mCRPC）与严重中性粒细胞减少症和 FN 的风险无关。
无论疾病状态如何，去势状态均不会影响接受多西他赛治疗的 mPCa 患者发生严重中性粒细胞减少症或 FN 的风险。未提供预防性治疗和患者年龄较大是严重中性粒细胞减少症的独立危险因素；而 PS 较差的患者更有可能发生 FN。这些发现可能有助于指导临床决策，以选择合适的多西他赛治疗候选者。
