Phase I dose-escalation study on irinotecan, cisplatin, and S-1 combination in chemotherapy-naive patients with HER2-negative advanced gastric cancer (HERBIS-4B, OGSG 1106)

BackgroundThe development of triplet regimens for advanced gastric cancer is challenging. The aim of this phase I dose-escalation study was to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naive patients with HER2-negative advanced gastric cancer.MethodsThe 3 + 3 design was adopted. Every 4 weeks, patients received an escalating dose of intravenous irinotecan (100-150 mg/m(2)) on day 1 and fixed doses of intravenous cisplatin (60 mg/m(2)) on day 1 and oral S-1 (80 mg/m(2)) on days 1 to 14.ResultsTwelve patients were enrolled in two dose level cohorts. In the level 1 cohort (irinotecan 100 mg/m(2), cisplatin 60 mg/m(2), and S-1 80 mg/m(2)), dose-limiting toxicity including grade 4 neutropenia and febrile neutropenia occurred in one of six patients, whereas in the level 2 cohort (irinotecan 125 mg/m(2), cisplatin 60 mg/m(2), and S-1 80 mg/m(2)), dose-limiting toxicities including grade 4 neutropenia developed in two of six patients. Thus, the level 1 and 2 doses were determined to be the recommended and maximum tolerated doses, respectively. Common grade 3 or higher adverse events were neutropenia (75%; n = 9), anemia (25%; n = 3), anorexia (8%; n = 1), and febrile neutropenia (17%; n = 2). Irinotecan, cisplatin, and S-1 combination therapy achieved an overall response rate of 67% with a median progression-free survival and overall survival of 19.3 and 22.4 months, respectively.ConclusionsThe potential treatment efficacy of this triplet regimen in HER2-negative advanced gastric cancer warrants further evaluation, especially in patients requiring intensive chemotherapy.

Automated summary

This study aimed to determine the maximum tolerated dose and recommended dose of the combination of irinotecan, cisplatin, and S-1 in chemotherapy-naive patients with HER2-negative advanced gastric cancer. The results showed that the triplet regimen achieved favorable treatment efficacy in HER2-negative advanced gastric cancer patients and may be a potential option for further treatment.