Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial

BMC Cancer

for the Dutch Pancreatic Cancer Group¹  J. de Vos-Geelen²  O. J. L. Loosveld³  J. W. Wilmink⁴  M. Y. V. Homs⁵  H. Bos⁶  G. van Tienhoven⁷  M. G. Besselink⁸  B. M. Zonderhuis⁹  I. H. J. T. de Hingh^1,10  Q. P. Janssen^1,11  J. L. van Dam^1,11  B. Groot Koerkamp^1,11  C. H. J. van Eijck^1,11  G. A. Patijn^1,12  K. P. Bosscha^1,13  B. A. Bonsing^1,14  P. P. L. O. Coene^1,15  M. S. L. Liem^1,16  T. M. Karsten^1,17  M. B. van der Kolk^1,18  H. C. van Santvoort^1,19 

[1] ;Department of Internal Medicine, Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht UMC+;Department of Medical Oncology, Amphia Hospital;Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Medical Oncology, Erasmus MC University Medical Center;Department of Medical Oncology, Tjongerschans Hospital;Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit;Department of Surgery, Catharina Hospital;Department of Surgery, Erasmus MC University Medical Center;Department of Surgery, Isala Hospital;Department of Surgery, Jeroen Bosch Hospital;Department of Surgery, Leiden University Medical Center;Department of Surgery, Maasstad Hospital;Department of Surgery, Medisch Spectrum Twente;Department of Surgery, Onze Lieve Vrouwe Gasthuis;Department of Surgery, Radboud University Medical Center;Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center Utrecht;

关键词: Neoadjuvant;    FOLFIRINOX;    Gemcitabine;    Chemoradiotherapy;    Localized pancreatic cancer;    Intention-to-treat;   

DOI  :  10.1186/s12885-021-08031-z

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown