Isaksson Jenny, Green Henrik, Papantoniou Dimitrios, Pettersson Linn, Anden Mats, Rosell Johan, Åvall-Lundqvist Elisabeth, Elander Nils Oskar
Department of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden.
Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden.
World J Clin Oncol. 2021 Nov 24;12(11):1009-1022. doi: 10.5306/wjco.v12.i11.1009.
The majority of patients with newly diagnosed metastatic prostate cancer (PC) initially respond to androgen deprivation therapy (ADT) and are classified as metastatic castration-sensitive PC (mCSPC). Following months to years of ADT, the disease tends to become resistant to ADT. Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC. Following its implementation in routine care, this combined treatment strategy requires more detailed evaluation in a real-world setting.
To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC.
A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed. This region includes approximately 1.1 million citizens and the oncology departments of Linköping, Jönköping, and Kalmar. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. The primary endpoint was progression-free survival (PFS) at 12 mo, and the secondary endpoints were PFS at 24 mo, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalizations. Exploratory analyses on potential prognostic parameters were performed.
Ninety-four patients were eligible and formed the study cohort. PFS at 12 and 24 mo was 75% (95%CI: 66-84) and 58% (46-70), respectively. OS at 12 and 24 mo was 93% (87-99) and 86% (76-96). A total of 91% of patients ( = 86) were given docetaxel according to the standard protocol of 75 mg/m every 3 wk (6 cycles), while 9% ( = 8) received a modified protocol of 50 mg/m every 2 wk (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate Cox regression analyses show that baseline PSA > 180 < 180 and the presence of distant metastases locoregional lymph node metastases were only negative prognostic factors (HR 2.86, 95%CI: 1.39-5.87, = 0.0041 and 3.36, 95%CI: 1.03-10.96, = 0.045). Following multivariate analysis, statistical significance remained for PSA (2.51, 95%CI: 1.21-5.19, = 0.013) but not for metastatic status (2.60, 95%CI: 0.78-8.65, = 0.12). Febrile neutropenia was recorded in 21% ( = 20) of patients, and 26% ( = 24) had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course.
Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.
大多数新诊断的转移性前列腺癌（PC）患者最初对雄激素剥夺疗法（ADT）有反应，被归类为转移性去势敏感性PC（mCSPC）。经过数月至数年的ADT治疗后，疾病往往会对ADT产生耐药性。最近的随机III期试验表明，在mCSPC中，在ADT基础上加用 upfront多西他赛可带来生存获益。在将其应用于常规治疗后，这种联合治疗策略需要在真实世界环境中进行更详细的评估。
评估 upfront多西他赛治疗mCSPC的真实世界疗效和安全性。
在瑞典东南部医疗保健地区进行了一项多中心回顾性队列研究。该地区约有110万居民，包括林雪平、延雪平和卡尔马的肿瘤科室。纳入了2015年7月至2017年12月期间所有接受 upfront多西他赛治疗mCSPC的患者。主要终点是12个月时的无进展生存期（PFS），次要终点是24个月时的PFS、总生存期（OS）、治疗强度、不良事件和非计划住院情况。对潜在的预后参数进行了探索性分析。
94例患者符合条件并组成研究队列。12个月和24个月时的PFS分别为75%（95%CI：66-84）和58%（46-70）。12个月和24个月时的OS分别为93%（87-99）和86%（76-96）。共有91%的患者（n = 86）按照每3周75 mg/m²（6个周期）的标准方案接受多西他赛治疗，而9%（n = 8）接受了每2周50 mg/m²（9个周期）的改良方案。开始标准治疗的患者的平均总剂量强度为91%。单因素Cox回归分析显示，基线前列腺特异性抗原（PSA）> 180 ng/ml vs < 180 ng/ml以及存在远处转移vs局部区域淋巴结转移只是阴性预后因素（HR 2.86，95%CI：1.39-5.87，P = 0.0041和3.36，95%CI：1.03-10.96，P = 0.045）。经过多因素分析后，PSA仍具有统计学意义（2.51，95%CI：1.21-5.19，P = 0.013），但转移状态无统计学意义（2.60，95%CI：0.78-8.65，P = 0.12）。21%（n = 20）的患者记录有发热性中性粒细胞减少，26%（n = 24）的患者在治疗过程中和治疗后30天内至少有一次非计划住院。
本研究结果支持将 upfront多西他赛加ADT作为mCSPC标准治疗策略的一部分实施。
