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The 2025 Dutch trial in which eight cycles of FOLFIRINOX before surgery, with no treatment afterwards, gave the same survival (about 22 months) as the older gemcitabine chemoradiotherapy schedule, so either can be used but neither is clearly better.
PREOPANC-2 enrolled 375 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma and WHO performance status 0 or 1 at 19 Dutch centres between June 2018 and January 2021, randomised 1:1 to eight cycles of neoadjuvant FOLFIRINOX followed by surgery without adjuvant treatment (188) or three cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, then surgery and four cycles of adjuvant gemcitabine (187). In the modified intention-to-treat population of 369, after a median follow-up of 42.3 months, median overall survival was 21.9 months with FOLFIRINOX versus 21.3 months with chemoradiotherapy (hazard ratio 0.88, 95 percent confidence interval 0.69 to 1.13, p = 0.32). Grade 3 to 4 neutropenia occurred in 25 versus 22 percent, diarrhoea in 23 versus 1 percent, leukopenia in 8 versus 15 percent; serious adverse events in 49 versus 43 percent; treatment-related deaths two versus one. Registered with EudraCT 2017-002036-17; funded by the Dutch Cancer Society and ZonMw.
Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.
Neoadjuvant treatment is now the standard for borderline resectable pancreatic cancer, and PREOPANC is the trial guidelines cite; the follow-on PREOPANC-2 tested FOLFIRINOX in the same setting.
The trial that made neoadjuvant treatment standard for borderline resectable disease and opened the still unresolved question for resectable disease, which PREOPANC-2, NORPACT-1, PREOPANC-3 and Alliance A021806 inherited.
Shares Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial, FOLFIRINOX / mFOLFIRINOX, Neoadjuvant / adjuvant / perioperative, Resectable pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Neoadjuvant / adjuvant / perioperative, Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Cytotoxic chemotherapy and the tag pancreatic-evidence.
Shares Resectable, borderline resectable and unresectable, Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Gemcitabine, Cytotoxic chemotherapy and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Trial design, endpoints and cost, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares FOLFIRINOX / mFOLFIRINOX, Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Resectable pancreatic ductal adenocarcinoma, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.