Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma: A GERCOR phase II study (FOXAGAST)

Background: 5-Fluorouracil (5-FU) and platinum-based perioperative chemotherapy is standard of care for resectable gastric adenocarcinoma (RGA). Nanoparticle albumin-bound (Nab-) paclitaxel is active in advanced disease but has never been evaluated in the perioperative setting. The objective was to evaluate the efficacy of Nab-paclitaxel in combination with FOLFOX for RGA patients. Methods: We performed a non-randomised, open-label, phase II study. RGA patients were assigned to receive neoadjuvant Nab-paclitaxel (150 mg/m(2)) and FOLFOX q2w for six cycles. Six additional post-operative cycles were kept at the investigator's discretion. The primary end-point was complete pathological response (tumour regression grade [TRG1]) rate. According to Fleming design, 49 patients were required to test H-0 (10% TRG1) and H-1 (25% TRG1). To reject H0, TRG1 had to be achieved in 8 patients. Results: Forty-nine patients were included. Median number of neoadjuvant chemotherapy cycles was 6 (range, 3-6). Median dose intensity for Nab-paclitaxel, oxaliplatin and 5-FU was 96% (38-103%), 97% (47-103%) and 99% (50-112%), respectively. Surgery could not be performed in 5 (10.2%) patients. Tumour resection was R0 for 42 of 44 (95.5%) patients. Pathological review classified tumours as TRG1 to TRG5 for 8 (16.3%), 11 (22.5%), 4 (8.2%), 18 (36.7%) and 3 (6.1%) patients, respectively. Grade 3 or worse toxicities during neoadjuvant chemotherapy were non-febrile neutropenia (20.4%), nausea (8.2%), diarrhoea (8.2%) and neuropathy (6.1%). Of 44 patients, 14 (31.8%) experienced surgery-related complications and three (6.8%) died of surgical complications. Conclusion: This regimen shows promising activity. Toxicity is manageable but a meaningful rate of surgical complications was observed. This strategy deserves investigation in phase III studies. (C) 2018 Elsevier Ltd. All rights reserved.