Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
BMC Cancer. 2021 Mar 23;21(1):300. doi: 10.1186/s12885-021-08031-z.
BACKGROUND: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. METHODS: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. DISCUSSION: The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. TRIAL REGISTRATION: Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004.
背景：新辅助治疗在局部胰腺癌患者中相对于直接手术具有几个潜在优势；更多的患者接受了系统治疗，更少的患者接受了无效手术，R0 切除率更高，从而可能提高总体生存率（OS）。两项最近的随机试验表明，新辅助放化疗优于直接手术，两者均包括单药化疗方案。潜在地，多药 FOLFIRINOX 方案（氟尿嘧啶+亚叶酸钙、伊立替康和奥沙利铂）可能进一步改善局部胰腺癌新辅助治疗的预后，但需要随机研究。PREOPANC-2 试验研究了新辅助 FOLFIRINOX 是否比新辅助吉西他滨为基础的放化疗和辅助吉西他滨更能改善可切除和边界可切除胰腺癌患者的 OS。
方法：这是一项全国多中心 III 期随机对照试验，纳入了经病理证实的可切除和边界可切除胰腺癌患者，这些患者的世界卫生组织表现评分为 0 或 1。可切除胰腺癌定义为无动脉和/或≤90 度静脉受累；边界可切除胰腺癌定义为≤90 度动脉和/或≤270 度静脉受累但无闭塞。患者接受 8 个周期的新辅助 FOLFIRINOX 化疗，然后不接受辅助治疗（A 组），或在第 2 个周期中接受 3 个周期的吉西他滨联合低分割放疗（36Gy，15 个分次），然后进行手术和 4 个周期的辅助吉西他滨（B 组）。主要终点是意向治疗的 OS。次要终点包括无进展生存期、生活质量、切除率和 R0 切除率。为了检测 80%效能下 0.70 的风险比，需要 252 个事件。预计在纳入 368 名符合条件的患者后，将达到事件数量，假设入组期为 3 年，随访期为 1.5 年。
讨论：PREOPANC-2 试验直接比较了两种新辅助方案在可切除和边界可切除胰腺癌患者中的应用。我们的研究将为可切除和边界可切除胰腺癌患者的新辅助治疗选择提供证据。
试验注册：主要登记处和试验识别号：EudraCT：2017-002036-17。登记日期：2018 年 3 月 6 日。次要识别号：荷兰国家试验登记处-NL7094，NL61961.078.17，MEC-2018-004。
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