D2 gastrectomy followed by postoperative S-1 is the standard therapy for the patients (pts) with stage III gastric cancer (GC) in East Asia, but 40% of the pts develop a recurrence. We hypothesize that the perioperative capecitabine and oxaliplatin (CapeOx) might improve survival for clinical stage III GC.
In this phase II trial, the eligibility criteria included pathologically confirmed clinical SS/SE N1-3 M0 GC according to Japanese Classification of GC (JCGC) 3rd English Edition. Perioperative CapeOx consisted of three cycles of CapeOx (capecitabine; 2,000 mg/m2 for 14 days, oxaliplatin; 130 mg/m2 day 1) every 3 weeks as neoadjuvant chemotherapy (CT), followed by five cycles of adjuvant CapeOx after the D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to JCGC (≥ Grade 1b). The planned sample size was 34 pts calculated on the hypothesis that the expected pRR was 65% and the threshold was 40%, with one-sided alpha of 0.05 and power of 90%.
Thirty-seven pts were enrolled from Apr. 2016 to May. 2017, and fully evaluated for efficacy and toxicity. R0 and R1 resection were achieved in 29 and three pts, respectively. One pt underwent R2 resection, and four pts could not undergo surgical resection. Sixteen pts underwent total gastrectomy, and 17 pts underwent distal gastrectomy. The pRR was 54.1% (one-sided p = 0.058, 95% CI: 36.9-70.5). The relative dose intensity (RDI) of Capecitabine and Oxaliplatin were 90.7% and 92.0%, respectively. Twenty-seven pts received adjuvant therapy, and the RDI of capecitabine and Oxaliplatin were 80.9% and 63.4%, respectively. Grade 3/4 toxicities of neoadjuvant CT included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%). Grade 3/4 toxicities of adjuvant CT included neutropenia (27%), diarrhea (8%), and anorexia (3%). Grade IIIa surgical complications included intraabdominal abscess (3%), bowel obstruction (3%), and anastomotic leakage (3%).
This phase II trial of perioperative CapeOx showed favorable antitumor activity with an acceptable safety profile for stage III GC, although pRR as primary endpoint did not meet the prespecified threshold.
Clinical trial identification
Legal entity responsible for the study
Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG).
Yakult Honsha Co., Ltd.
D. Sakai: Belongs to a donated fund laboratory: Yakult Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd. T. Satoh: Honoraria, Consulting fee: Eli Lilly, Chugai, Merck Serono; Research funding (institution): Sanofi, Yakult Honsha, Chugai, Ono. All other authors have declared no conflicts of interest.