Abstract 3719: Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: Clinical and pharmacogenetic results
Authors: Sook Ryun Park, Sun-Young Kong, Hyo Jin Cho, Young Lan Park, Jun Ho Lee, Keun Won Ryu, Young-Woo Kim, Il Ju Choi, Chan Gyoo Kim, Jong Yeul Lee, Soo-Jeong Cho, Jong Seok Lee, Myeong-Cherl Kook, Young-Iee Park, Keun-Wook Lee, Noe Kyeong Kim
Journal: Cancer Research (2010)

Abstract Introduction: This study investigated the efficacy and safety of S-1 plus irinotecan and oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and examined the association between uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms and treatment outcomes. Methods: Patients with previously untreated MGC received S-1 40 mg/m2 b.i.d. on days 1-14, irinotecan 150 mg/m2 and oxaliplatin 85 mg/m2 on day 1 every 3 weeks. We analyzed the association of UGT1A genotypes and clinical outcomes. Results: Forty-four patients were enrolled on study and received a median of 11 cycles (range, 1-12). Of the 42 patients assessable for response, the objective response rate was 79% (95% CI, 66% to 91%); complete response (CR) (14%) and partial response (64%). The median time to progression (TTP) and overall survival (OS) was 10.2 months (95% CI, 7.7 to 12.7) and 17.6 months (95% CI, 9.0 to 26.2), respectively. Ten (26%) of 39 patients with primary gastric tumor showed a biopsy-proven gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. Non-hematological toxicities were modest and manageable. The most common grade 3 non-hematological toxicity was abdominal pain (18%), followed by anorexia (16%) and diarrhea (14%). UGT1A polymorphisms was associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, or UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), or grade 3 abdominal pain (UGT1A1*6). Conclusions: TIROX is a highly active regimen inducing marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. Genotyping for UGT1A might predict severe toxicity for TIROX.Association of UGT1A Genotypes with Toxicity during Cycle 1 G4 leukopeniaG4 neutropeniaG3/4 febrile neutropeniaG3 abdominal pain No.(%)PNo.(%)PNo.(%)PNo.(%)PUGT1A1*6 0.042 0.013 0.042 0.042absence0/28 (0) 0/28 (0) 0/28 (0) 0/28 (0) presence3/16 (19) 4/16 (25) 3/16 (19) 3/16 (19) UGT1A1*28 1.000 1.000 1.000 1.000absence3/35 (9) 3/35 (9) 3/35 (9) 3/35 (9) presence0/9 (0) 1/9 (11) 0/9 (0) 0/9 (0) UGT1A1*60 0.258 0.634 0.258 0.258absence3/26 (12) 3/26 (12) 3/26 (12) 3/26 (12) presence0/18 (0) 1/18 (6) 0/18 (0) 0/18 (0) UGT1A6*2 0.100 0.044 0.100 0.100absence0/23 (0) 0/23 (0) 0/23 (0) 0/23 (0) presence3/21 (14) 4/21 (19) 3/21 (14) 3/21 (14) UGT1A7*3 0.100 0.044 0.100 0.100absence0/23 (0) 0/23 (0) 0/23 (0) 0/23 (0) presence3/21 (14) 4/21 (19) 3/21 (14) 3/21 (14) Toxicity grade by National Cancer Institute Common Toxicity Criteria version 3.0 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3719.