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Table of Contents
Vol. 82, No. 5, 2012
Issue release date: May 2012
Section title: Clinical Study
Oncology 2012;82:290–297
(DOI:10.1159/000337989)

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 Y.H.a · Kim T.W.a · Kim K.-P.a · Lee S.S.a · Hong Y.S.a · Ryu M.-H.a · Lee J.-L.a · Chang H.M.a · Ryoo B.-Y.a · Kim H.-S.b · Shin J.-G.b · Kang Y.-K.a
aDepartment of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, and bDepartment of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine and Clinical Pharmacology Center, Busan Paik Hospital, Busan, Korea

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Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 12/29/2011 8:34:12 PM
Accepted: 3/12/2012
Published online: 4/28/2012
Issue release date: May 2012

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL

Abstract

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/m2) on day 1 and S-1 (80 mg/m2) 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.

© 2012 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Clinical Study

Received: 12/29/2011 8:34:12 PM
Accepted: 3/12/2012
Published online: 4/28/2012
Issue release date: May 2012

Number of Print Pages: 8
Number of Figures: 1
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: http://www.karger.com/OCL


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