Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002).

"Conflict of interest Chikuma Hamada has received advisory fees from Yakult Honsha Co., Ltd. (Tokyo, Japan) and Daiichi Sankyo Co., Ltd. (Tokyo, Japan). Yuh Sakata has received advisory fees and honoraria from Yakult Honsha Co., Ltd. (Tokyo, Japan), Daiichi Sankyo Co., Ltd. (Tokyo, Japan), and Taiho Pharmaceutical Co., Ltd. (Tokyo, Japan). The other authors have no conflicts of interest to declare."

"This study was supported by Yakult Honsha Co., Ltd. and Daiichi Sankyo Co., Ltd. (GC0301/TOP002). The funding source had no role in the study design, data collection, data analysis, or interpretation. We thank the patients, clinicians, and support staff who participated in this study. We also thank Y. Takada, K. Miyakawa, and K. Tamura for performing extramural review to assess objective responses, as well as T. Taguchi, S. Yoshida, and H. Origasa for their helpful advice."

"The eligibility criteria were histologically and cytologically confirmed unresectable or recurrent gastric adenocarcinoma; oral food intake possible; age between 20 and 75 years; no prior radiotherapy or chemotherapy; expected survival for ≥12 weeks; Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; and adequate major organ function before chemotherapy (leukocyte count of 4,000–12,000/mm3, hemoglobin ≥ 8.0 g/dl, platelet count ≥ 100,000/mm3, total bilirubin ≤ 1.5 mg/dl, aspartate aminotransferase ≤ 100 IU/l, alanine aminotransferase ≤ 100 IU/l, creatinine ≤ 1.2 mg/dl). The main exclusion criteria were massive ascites, active concomitant malignancy, uncontrolled diabetes mellitus, and pregnancy or breast-feeding. Written informed consent was obtained from each patient. Institutional review board approval was obtained at each participating institution. An independent data monitoring committee evaluated safety throughout this study. The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. This trial was registered with the Japan Pharmaceutical Information Center (JapicCTI-050083)."