Facchini Gaetano, Caffo Orazio, Ortega Cinzia, D'Aniello Carmine, Di Napoli Marilena, Cecere Sabrina C, Della Pepa Chiara, Crispo Anna, Maines Francesca, Ruatta Fiorella, Iovane Gelsomina, Pisconti Salvatore, Montella Maurizio, Berretta Massimiliano, Pignata Sandro, Cavaliere Carla
Division of Medical Oncology, Department of Uro-Gynaecological Oncology, Istituto Nazionale Tumori "Fondazione G. Pascale" - IRCCS Naples, Italy.
Department of Medical Oncology, Santa Chiara Hospital Trento, Italy.
Front Pharmacol. 2016 May 18;7:123. doi: 10.3389/fphar.2016.00123. eCollection 2016.
Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting.
We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics.
We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days.
A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.
醋酸阿比特龙（AA）被批准用于治疗在雄激素剥夺治疗失败后且尚未有临床化疗指征的转移性去势抵抗性前列腺癌（mCRPC），以及用于治疗在基于多西他赛的化疗方案期间或之后进展的mCRPC。本研究的目的是评估在化疗后接受AA治疗的mCRPC患者中，早期前列腺特异性抗原（PSA）下降对于检测治疗成功或失败的作用。
我们回顾性评估了87例接受AA治疗的mCRPC患者。在15天、90天后评估血清PSA水平，之后每月评估一次。根据至少间隔1周的确认值评估PSA flare现象。主要终点是证明早期PSA下降与更长的无进展生存期（PFS）和总生存期（OS）相关。次要终点是证明更好的结局与患者的人口统计学和临床特征之间的相关性。
我们收集了2011年9月至2014年9月期间87例患者的数据。在接受评估的患者中，56%出现早期PSA反应（在15天时较基线下降≥50%），90天后在29例患者中得到确认。中位PFS为5.5个月（4.6 - 6.5），中位OS为17.1个月（8.8 - 25.2）。在早期反应者（15天时PSA反应率≥50%）中，我们发现在1年的PFS方面有显著的统计学优势，风险比（HR）为0.28，95%置信区间（CI）为0.12 - 0.65，p = 0.003；在OS方面，HR为0.21，95%CI为0.06 - 0.72，p = 0.01。在90天评估时，1年PFS和OS的结果也达到了统计学显著性。
很大一部分（78.6%）患者在PSA下降方面实现了快速反应。早期PSA反应率（开始使用AA后15天时≥50%）可提供具有临床意义的信息，并可被视为更长PFS和OS的替代指标。
