Phase II study of docetaxel (DTX) and S-1 as neoadjuvant chemotherapy for potentially R0 advanced gastric cancer.

Abstract

74 Background: This trial sought to evaluate the efficacy and safety of preoperative chemotherapy with DTX plus S-1 for advanced gastric cancer with poor prognosis even after R0 curative resection. We show the 2 years follow-up data. Methods: Preoperative staging was confirmed by laparoscopy. Eligibility criteria included 1) negative peritoneal cytology, H0, P0 and M0, 2) possible curative resection, and 3) ECOG PS 0-1. Patients received DTX (35 mg/m2) on days 1 and 15, and daily oral administration of S-1 (80 mg/m2/day) for days 1–14 every 4 weeks of 2 courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). A sample size of 45 was planned for the expected pRR of 40% and threshold value of 20%, with one-sided alpha of 0.05 and beta of approximately 0.1. Results: A total of 47 patients were centrally registered between November 2007 and November 2009 from 14 centers. All patients were eligible for analysis. The median age was 63 (range 37–79); male/female: 36/11; PS0/1:41/6; and clinical stage IIIA/IIIB: 31/16. The target pRR was 47% (90%CI, 34–60%; p<0.0001). Forty six patients (98%) underwent surgery, in whom curative resection was performed in 44 patients, and 37 patients completed the protocol treatment. The response to preoperative chemotherapy was PR/SD/PD/NE in 16/24/2/5 with a response rate of 34%. The rate of 2 years and 3 years DFS were 53.9%, and 49.3%, respectively. The rate of 2 years and 3 years Overall survival were 69.6%, and 55.1%, respectively. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42%), febrile neutropenia (4%), grade 2 anorexia (21%), and fatigue (15%). Major operative morbidity included pancreatic fistula (9%), abdominal abscess (11%), pneumonia (2%), and anastomotic leakage (0%). No patients died due to surgical complications. Conclusions: The combination of DTX and S-1 was well tolerated and promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer. Clinical trial information: UMIN000000875.