接受标准剂量及减量的每三周一次多西他赛治疗转移性去势抵抗性前列腺癌的男性发生发热性中性粒细胞减少及早期治疗中断的风险
Risk of febrile neutropenia and early treatment cessation in men receiving standard and dose-reduced 3-weekly docetaxel for metastatic castration-resistant prostate cancer.
作者信息
Hamid Anis A, Willson Kaspar, Vincent Andrew D, Tamjid Babak, Lee Margaret, Bergin Alice, Gan Chun, Campbell Ainsley, Stewart Josephine, Pezaro Carmel, Tran Ben, Weickhardt Andrew J
机构信息
Olivia Newton-John Cancer Wellness and Research Center, Austin Hospital, Heidelberg, Victoria, Australia.
Freemasons Foundation Center for Men's Health, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
出版信息
Asia Pac J Clin Oncol. 2018 Oct;14(5):e399-e404. doi: 10.1111/ajco.12840. Epub 2018 Jan 10.
BACKGROUND
Docetaxel is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC); however, many patients experience febrile neutropenia (FN) and cease treatment early due to toxicity. It is not known whether lower dose (LD) q3-weekly docetaxel impacts toxicity or efficacy.
METHODS
Multicenter retrospective study included 166 patients with mCRPC who received q3-weekly docetaxel between 2010 and 2015. Demographic, disease, chemotherapy (standard dose, SD 60 mg/m vs LD 60 mg/m ) and toxicity data were collected. Univariable and multivariable logistic and competing risk regression models evaluated docetaxel-dose association with FN and early treatment cessation (ETC) due to toxicity. Associations between dose and efficacy end points were also evaluated. Analyses were repeated employing inverse propensity score weights.
RESULTS
Patients who received LD docetaxel (28.9%) were older with poorer Eastern Cooperative Oncology Group (ECOG) status. Fifteen percent of patients experienced FN, with a nonsignificant trend to lower incidence in the LD group (multiple adjusted odds ratio [OR] = 0.42; P = 0.21). Neither baseline patient nor prior treatment factors were predictive of FN. ETC due to toxicity occurred in 35%, with risk associated with increasing age, comorbidity count and poorer ECOG. There was no difference between LD and SD with respect to ETC due to toxicity, in unweighted and weighted analyses (LD vs SD, multivariable weighted hazard ratio [HR] = 1.47; P = 0.08). LD was associated with reduced prostate-specific antigen (PSA) response (50% vs 66.1%, multivariable weighted HR = 0.54; P = 0.03) and overall survival (median 7.9 vs 13.8 months, multivariable weighted HR = 2.19; P < 0.0001).
CONCLUSIONS
LD docetaxel for mCRPC did not mitigate the risk of FN or ETC due to toxicity. Dose reduction may result in poorer PSA response and survival.
背景
多西他赛是转移性去势抵抗性前列腺癌（mCRPC）的一种有效治疗方法；然而，许多患者会出现发热性中性粒细胞减少（FN），并因毒性而提前停止治疗。尚不清楚每3周一次的低剂量（LD）多西他赛是否会影响毒性或疗效。
方法
多中心回顾性研究纳入了2010年至2015年间接受每3周一次多西他赛治疗的166例mCRPC患者。收集了人口统计学、疾病、化疗（标准剂量，SD 60mg/m²对比LD 60mg/m²）和毒性数据。单变量和多变量逻辑回归及竞争风险回归模型评估了多西他赛剂量与FN以及因毒性导致的早期治疗中断（ETC）之间的关联。还评估了剂量与疗效终点之间的关联。采用逆倾向评分权重重复进行分析。
结果
接受LD多西他赛治疗的患者（28.9%）年龄较大，东部肿瘤协作组（ECOG）状态较差。15%的患者出现FN，LD组的发病率有降低趋势，但无统计学意义（多重校正比值比[OR]=0.42；P=0.21）。基线患者因素和既往治疗因素均不能预测FN。因毒性导致的ETC发生率为35%，风险与年龄增加、合并症数量和较差的ECOG状态相关。在未加权和加权分析中，LD组和SD组因毒性导致的ETC无差异（LD对比SD，多变量加权风险比[HR]=1.47；P=0.08）。LD与前列腺特异性抗原（PSA）反应降低相关（50%对比66.1%，多变量加权HR=0.54；P=0.03）以及总生存期降低相关（中位生存期7.9个月对比13.8个月，多变量加权HR=2.19；P<0.0001）。
结论
用于mCRPC的LD多西他赛并未降低因毒性导致的FN或ETC风险。剂量降低可能导致PSA反应和生存期较差。
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