Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer

Background: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. Methods: Irinotecan 125 mg/m(2) on day 1 and cisplatin 60 mg/m 2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. Results: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m(2). Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m(2) and cisplatin 50 mg/m(2). The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan lowdose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. Conclusions: The combination of biweekly irinotecan 80 mg/m(2) and cisplatin 50 mg/m 2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation. (C) 2016 S. Karger AG, Basel