A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced gastric cancer.

Abstract

4057 Background: We have previously reported that phase II studies of combination chemotherapy with docetaxel, cisplatin and S-1 (DCS) demonstrated a very high response rate (87.1%) and a promising survival time (MST 687 days) in patients with unresectable advanced gastric cancer (BJC 2008, CCP 2009). This regimen showed no case of PD and an appreciable rate of downstaging, suggesting the applicability of DCS to neoadjuvant chemotherapy (NAC). We therefore conducted a multicenter phase II trial to evaluate the efficacy and safety of neoadjuvant DCS for locally advanced gastric cancer. Methods: The study included patients (pts) with histologic confirmation of gastric cancer, no prior chemotherapy, adequate organ function, PS 0-1, age 20-80, and clinical stages of cT3-4, cN0-3, and cM0 (Japanese staging system). S-1 80 mg/m2 was administered orally on days 1-14, followed by intravenous administration of cisplatin 60 mg/m2on day 8, and docetaxel 60 mg/m2on day 8. All pts received 2 courses of treatment every 3 weeks and responders received a maximum of 4 courses, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability and the secondary endpoints included response rate, histological response, survival time, and safety. Results: From July 2006 to November 2010, 40 pts (median age 66, male/female 28/12, PS0/1 29/11) were enrolled. The median number of courses received was 2 (1-4). Response rate was 71.8% with 29 PR and 11 SD cases. Grade 3/4 adverse events were leukopenia (55.0%), neutropenia (55.0%), febrile neutropenia (17.5%), diarrhea (22.5%), anorexia (25.0%), and nausea (17.5%), but they were generally transient and manageable. Curative surgery was performed in 39 pts; 36 pts (92.3%) underwent R0 resection. Downstaging was achieved in 26 pts and pathological response was found in 24 pts. There were no treatment-related deaths and no major surgical complications. Conclusions: Neoadjuvant DCS chemotherapy demonstrated a high response rate and a sufficient R0 resection rate for locally advanced gastric cancer with manageable toxicities. The results suggested the efficacy of DCS regimen in the neoadjuvant setting.