Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
In Vivo. 2021 Nov-Dec;35(6):3509-3519. doi: 10.21873/invivo.12653.
BACKGROUND/AIM: Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC.
We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival.
Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group.
The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.
背景/目的:多西紫杉醇已在转移性去势抵抗性前列腺癌(mCRPC)患者中广泛使用了数十年。本研究的目的是评估多西紫杉醇在 mCRPC 患者中的再挑战疗效。
我们回顾性比较了接受一线多西紫杉醇治疗并在雄激素受体轴靶向治疗(ARAT)后进行再挑战的患者与未进行多西紫杉醇再挑战的患者。采用多变量 cox 回归分析评估生存情况。
在纳入本研究的 204 例 mCRPC 患者中,24 例患者接受了多西紫杉醇再挑战,180 例患者未接受再挑战。再挑战组的中位总生存期为 50.11 个月,而非再挑战组为 26.36 个月(对数秩检验的 p 值=0.044)。在多变量模型中,多西紫杉醇再挑战是总生存期的独立危险因素[风险比(HR)=0.59,95%置信区间(CI)=0.32-0.99],与体能状态评分 2(HR=2.46,95%CI=1.32-4.58)、激素敏感状态持续时间(HR=0.99,95%CI=0.99-0.999)、肝转移(HR=1.90,95%CI=1.04-3.47)和脑转移(HR=2.23,95%CI=1.26-5.46)有关。在雄激素受体轴靶向(ARAT)无反应的患者中,再挑战的优势明显(HR=0.36,95%CI=0.17-0.78)。多西紫杉醇再挑战组不良反应发生率为 29.17%,其中 3/4 级中性粒细胞减少症为 20.83%,1/2 级中性粒细胞减少症为 20.83%。
多西紫杉醇再挑战可提高一线多西紫杉醇治疗后失败的 mCRPC 患者以及后续阿比特龙或恩杂鲁胺的生存。总生存期的独立预测因素包括:i)体能状态;ii)激素敏感状态持续时间;iii)肝转移;iv)脑转移。对 ARAT 无反应的患者将从多西紫杉醇再挑战中获益,提高总生存期。