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1. Oncology. 2012 Apr 28;82(5):290-297. [Epub ahead of print]

A Phase II Study of Clinical Outcomes of 3-Week Cycles of Irinotecan and S-1 in
Patients with Previously Untreated Metastatic Colorectal Cancer: Influence of the
UGT1A1 and CYP2A6 Polymorphisms on Clinical Activity.

Choi YH, Kim TW, Kim KP, Lee SS, Hong YS, Ryu MH, Lee JL, Chang HM, Ryoo BY, Kim
HS, Shin JG, Kang YK.

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.

Copyright © 2012 S. Karger AG, Basel.

PMID: 22555197 [PubMed - as supplied by publisher]