S Watson1, C de la Fouchardière2, S Kim3, R Cohen4, J B Bachet5, C Tournigand6, J M Ferraz7, M Lefevre8, D Colin8, M Svrcek9, A Meurisse10, C Louvet11. 1. Medical Oncology Department, Institut Mutualiste Montsouris, Paris, France. 2. Medical Oncology Department, Centre Léon Bérard, Lyon, France. 3. Medical Oncology Department, Centre Hospitalier Régional Universitaire, Besançon, France. 4. Sorbonne Université, Medical Oncology Department, AP-HP, hôpital Saint-Antoine, F-75012 Paris, France. 5. Sorbonne Universités, UPMC, Gastro-enterology Department, Hôpital de la Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France. 6. Medical Oncology Department, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris, UPEC, Créteil, France. 7. Surgical Department, Institut Mutualiste Montsouris, Paris, France. 8. Pathology Department, Institut Mutualiste Montsouris, Paris, France. 9. Sorbonne Université, UPMC, Pathology Department, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, Paris, France. 10. Methodological and Quality of Life in Oncology Unit, Centre Hospitalier Régional Universitaire, Besançon, France. 11. Medical Oncology Department, Institut Mutualiste Montsouris, Paris, France. Electronic address: christophe.louvet@imm.fr.
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/m2) 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.
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/m2) 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.
Authors: Alexander P Stark; Mariela M Blum; Yi-Ju Chiang; Prajnan Das; Bruce D Minsky; Jeannelyn S Estrella; Jaffer A Ajani; Brian D Badgwell; Paul Mansfield; Naruhiko Ikoma Journal: J Gastric Cancer Date: 2020-09-17 Impact factor: 3.720