M Y V Homs1, G van Tienhoven2, M G Besselink3, J W Wilmink4, Q P Janssen5, J L van Dam5, B A Bonsing6, H Bos7, K P Bosscha8, P P L O Coene9, C H J van Eijck5, I H J T de Hingh10, T M Karsten11, M B van der Kolk12, G A Patijn13, M S L Liem14, H C van Santvoort15, O J L Loosveld16, J de Vos-Geelen17, B M Zonderhuis18, B Groot Koerkamp19. 1. Department of Medical Oncology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 2. Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 3. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 4. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 5. Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 6. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. 7. Department of Medical Oncology, Tjongerschans Hospital, Heerenveen, The Netherlands. 8. Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands. 9. Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands. 10. Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands. 11. Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. 12. Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands. 13. Department of Surgery, Isala Hospital, Zwolle, The Netherlands. 14. Department of Surgery, Medisch Spectrum Twente, Enschede, The Netherlands. 15. Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center Utrecht, Utrecht, The Netherlands. 16. Department of Medical Oncology, Amphia Hospital, Breda, The Netherlands. 17. Department of Internal Medicine, Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, The Netherlands. 18. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands. 19. Department of Surgery, Erasmus MC University Medical Center, Rotterdam, The Netherlands. b.grootkoerkamp@erasmusmc.nl.
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.
RCT Entities:
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 cancerpatients. 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.
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