A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study
A single-arm, phase II trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study
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DOI：
10.1007/s00535-018-1506-7
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发表时间：
2019-02-01
影响因子：
6.3
通讯作者：
Ottomo, S.
中科院分区：
文献类型：
--
作者：
Motoi, Fuyuhiko;Satoi, Sohei;Ottomo, S.
新辅助化疗(NAC)是胰腺导管腺癌(PDAC)计划切除的一种有前途的替代方案，但其对生存的影响尚不明确。通过前瞻性研究，评价NAC联合吉西他滨和S1(GS)治疗PDAC的可行性和生存效果。方法对可切除或边缘可切除的PDAC患者进行2个周期的NAC-GS治疗，并给予根治性切除和吉西他滨辅助治疗。主要终点是2年总生存期(OS)。NAC期间的不良事件、放射学和肿瘤标志物反应、切除率和手术安全性被评估为次要终点(UMIN000004148)。结果我们纳入了2010-2012年间的104名患者，其中101名患者使用NAC-GS作为完整分析集(Fas)。在101名患者中，88%的患者接受了计划的2个周期的NAC。中性粒细胞减少以3级多见(35%)。放射部分反应和糖类抗原19-9浓度降低(>；50%)分别为13%和41%。65例患者行R0/1切除加M0手术，无手术死亡。在65名患者中，44名患者接受了为期6个月的吉西他滨计划辅助治疗，作为方案队列。2年OS率的主要终点在Fas组(n=101)为55.9%，在方案队列组(n=44)为74.6%。结论NAC-GS在PDAC计划切除后是可行的，并能积极延长生存期。除了手术和辅助治疗外，还需要随机对照试验来进一步阐明NAC-GS的生存益处。
BackgroundNeoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.MethodsPatients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).ResultsWe enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (>50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n=101) and 74.6% in the on-protocol cohort (n=44).ConclusionsNAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.