A Phase II Study of Clinical Outcomes of 3-Week Cycles of Irinotecan and S-1 in Patients with Previously Untreated Metastatic Colorectal Cancer
Choi YH et al. – The results indicate that irinotecan (CPT–11) and S–1 (IRIS) is a promising first–line regimen in patients with metastatic colorectal cancer. Severe neutropenia may be associated with interindividual variations in UGT1A1 polymorphisms.Methods
- The patients received CPT-11 (225mg/m2) on day 1 and S-1 (80mg/m2) on days 1–14 every 3weeks.
- The association of the UGT1A1 (*6 and *28) and CYP2A6(*4, *7, *9, and *10) polymorphisms with toxicities and efficacy were analyzed.
- Thirty patients were treated.
- The overall response rate was 66.7% (95% CI 48.7-84.6).
- The median time to progression was 7.6months (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.