Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial

Background Patients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy.The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery.Methods ESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany).Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review.Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m² on days 1, 8, and 15, and oral capecitabine 830 mg/m² twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², folinic acid given according to local practice, and fluorouracil 400 mg/m² bolus injection on days 1 and 15 followed by 2400 mg/m² 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50•4 Gy in 28 daily fractions over 5•5 weeks [1•8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m² twice daily [Monday to Friday] throughout radiotherapy).Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable.All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion.Primary endpoints were recruitment rate and resection rate.Analyses were done on an intention-to-treat basis.This trial is registered with ISRCTN, 89500674, and is complete.