Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma: A GERCOR phase II study (FOXAGAST). (January 2019)

• Record Type: Journal Article
• Authors: Watson, S.; de la Fouchardière, C.; Kim, S.; Cohen, R.; Bachet, J.B.; Tournigand, C.; Ferraz, J.M.; Lefevre, M.; Colin, D.; Svrcek, M.; Meurisse, A.; Louvet, C.
• Is Part Of: European journal of cancer. Volume 107(2019)
• Page Start: 46
• Page End: 52
• Publication Date: 2019-01
• Subjects: Gastric cancer -- Nab-paclitaxel -- Neoadjuvant chemotherapy -- Tumour regression grade; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.11.006
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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 H0 (10% TRG1) and H1 (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. Highlights: Neoadjuvant FOXAGAST leads to major cPR rate in resectable oesogastric adenocarcinoma. Patients treated with FOXAGAST as perioperative regimen show prolonged PFS and OS. FOXAGAST regimen is associated with a high rate of surgical complications.