Kongsted Per, Svane Inge Marie, Lindberg Henriette, Sengeløv Lisa
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Clin Genitourin Cancer. 2016 Dec;14(6):e559-e568. doi: 10.1016/j.clgc.2016.03.018. Epub 2016 Mar 24.
In the present study, we examined possible predictors of chemotherapy-induced toxicity, treatment outcomes, and the consequences of dose reductions in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving standard docetaxel.
Medical records from 421 consecutive patients treated with first-line docetaxel (75 mg/m every 3 weeks) and low-dose prednisolone from 2007 to 2013 at Herlev University Hospital were reviewed. Common Terminology Criteria for Adverse Events, version 4.0, and the Prostate Cancer Working Group 2 guidelines were used to evaluate treatment-related toxicity and efficacy. Logistic and Cox regression models were used to predict toxicity and survival.
Age ≥ 75 years (odds ratio [OR], 2.33), baseline levels of hemoglobin (OR, 0.89), and previous metastatic epidural spinal cord compression (MESCC; OR, 1.70) were predictive of grade 3 and 4 nonhematologic toxicity. Previous MESCC was associated with a greater risk of febrile neutropenia (OR, 2.74). The median progression-free survival (PFS) and overall survival (OS) were 6.4 and 15.4 months, respectively. Survival was similar in the older (age ≥ 75 years) and younger patients (P = .66, P = .90; log-rank) and when comparing patients undergoing dose reductions with patients treated with standard docetaxel throughout their treatment course (P = .51 and P = 0.52; log-rank). A longer interval from the primary diagnosis to the initiation of docetaxel (hazard ratio [HR], 1.00), baseline hemoglobin levels (HR, 0.85), Eastern Cooperative Oncology Group performance status > 0 to 1 (HR, 1.44), lactate dehydrogenase greater than the upper limit of normal (HR, 1.64), and prostate-specific antigen levels (HR, 1.00) were predictors of OS.
OS in the everyday clinical setting was inferior to that observed in randomized trials. Our results indicate that elderly patients and patients with moderate anemia or a history of MESCC at baseline have a greater risk of treatment-induced toxicity. Dose reductions did not compromise survival.
在本研究中，我们调查了接受标准多西他赛治疗的转移性去势抵抗性前列腺癌（mCRPC）患者化疗诱导毒性的可能预测因素、治疗结果以及剂量降低的后果。
回顾了2007年至2013年在赫勒夫大学医院接受一线多西他赛（每3周75mg/m²）和低剂量泼尼松龙治疗的421例连续患者的病历。采用不良事件通用术语标准4.0版和前列腺癌工作组2指南评估治疗相关毒性和疗效。使用逻辑回归和Cox回归模型预测毒性和生存情况。
年龄≥75岁（比值比[OR]，2.33）、血红蛋白基线水平（OR，0.89）以及既往转移性硬膜外脊髓压迫（MESCC；OR，1.70）可预测3级和4级非血液学毒性。既往MESCC与发热性中性粒细胞减少风险增加相关（OR，2.74）。中位无进展生存期（PFS）和总生存期（OS）分别为6.4个月和15.4个月。年龄较大（≥75岁）和较年轻患者的生存情况相似（P = 0.66，P = 0.90；对数秩检验），在比较整个治疗过程中接受剂量降低治疗的患者与接受标准多西他赛治疗的患者时也是如此（P = 0.51和P = 0.52；对数秩检验）。从初次诊断到开始使用多西他赛的间隔时间较长（风险比[HR]，1.00）、血红蛋白基线水平（HR，0.85）、东部肿瘤协作组体能状态>0至1（HR，1.44）、乳酸脱氢酶高于正常上限（HR，1.64）以及前列腺特异性抗原水平（HR，1.00）是OS的预测因素。
日常临床环境中的OS低于随机试验中观察到的情况。我们的结果表明，老年患者以及基线时有中度贫血或MESCC病史的患者发生治疗诱导毒性的风险更高。剂量降低并未影响生存。
