OBJECTIVES: We investigated the efficacy and safety of the combination of irinotecan (CPT-11) and S-1 (IRIS regimen) as a first-line treatment in patients with metastatic colorectal cancer. We also evaluated the association between UGT1A1 and CYP2A6 polymorphisms and clinical phenotypes. METHODS: The patients received CPT-11 (225 mg/m(2)) on day 1 and S-1 (80 mg/m(2)) on days 1-14 every 3 weeks. The association of the UGT1A1 (*6 and *28) and CYP2A6(*4, *7, *9, and *10) polymorphisms with toxicities and efficacy were analyzed. RESULTS: Thirty patients were treated. The overall response rate was 66.7% (95% CI 48.7-84.6). The median time to progression was 7.6 months (95% CI 5.8-9.5). The most common grade 3/4 hematologic and non-hematologic toxicity were neutropenia (53.4%) and diarrhea (16.7%), respectively. The allele frequencies of UGT1A1*6 and *28 were 15.5 and 10.3%, respectively. The frequencies of CYP2A6*4, *7, *9, and *10 were 15.5, 8.6, 29.3, and 3.5%, respectively. Stratification of patients according to the number of UGT1A1*28 and *6 alleles showed a significant correlation between the number of defective alleles and the incidence of grade 3/4 neutropenia. CONCLUSIONS: Our results indicate that IRIS is a promising first-line regimen in patients with metastatic colorectal cancer. Severe neutropenia may be associated with interindividual variations in UGT1A1 polymorphisms.
OBJECTIVES: We investigated the efficacy and safety of the combination of irinotecan (CPT-11) and S-1 (IRIS regimen) as a first-line treatment in patients with metastatic colorectal cancer. We also evaluated the association between UGT1A1 and CYP2A6 polymorphisms and clinical phenotypes. METHODS: The patients received CPT-11 (225 mg/m(2)) on day 1 and S-1 (80 mg/m(2)) on days 1-14 every 3 weeks. The association of the UGT1A1 (*6 and *28) and CYP2A6(*4, *7, *9, and *10) polymorphisms with toxicities and efficacy were analyzed. RESULTS: Thirty patients were treated. The overall response rate was 66.7% (95% CI 48.7-84.6). The median time to progression was 7.6 months (95% CI 5.8-9.5). The most common grade 3/4 hematologic and non-hematologic toxicity were neutropenia (53.4%) and diarrhea (16.7%), respectively. The allele frequencies of UGT1A1*6 and *28 were 15.5 and 10.3%, respectively. The frequencies of CYP2A6*4, *7, *9, and *10 were 15.5, 8.6, 29.3, and 3.5%, respectively. Stratification of patients according to the number of UGT1A1*28 and *6 alleles showed a significant correlation between the number of defective alleles and the incidence of grade 3/4 neutropenia. CONCLUSIONS: Our results indicate that IRIS is a promising first-line regimen in patients with metastatic colorectal cancer. Severe neutropenia may be associated with interindividual variations in UGT1A1 polymorphisms.
Authors: Sollip Kim; Yeo Min Yun; Hyo Jin Chae; Hyun Jung Cho; Misuk Ji; In Suk Kim; Kyung A Wee; Woochang Lee; Sang Hoon Song; Hye In Woo; Soo Youn Lee; Sail Chun Journal: Ann Lab Med Date: 2017-03 Impact factor: 3.464