Brief Article
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 28, 2009; 15(40): 5058-5066
Published online Oct 28, 2009. doi: 10.3748/wjg.15.5058
UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer
Christoph Schulz, Volker Heinemann, Andreas Schalhorn, Nikolas Moosmann, Thomas Zwingers, Stefan Boeck, Clemens Giessen, Hans-Joachim Stemmler
Christoph Schulz, Volker Heinemann, Andreas Schalhorn, Nikolas Moosmann, Stefan Boeck, Clemens Giessen, Hans-Joachim Stemmler, Department of Haematology & Oncology, Ludwig-Maximilians University of Munich, Campus Grosshadern, Marchioninistr 15, Munich 81377, Germany
Thomas Zwingers, Estimate GmbH, Konrad-Adenauer-Allee 1, Augsburg 86150, Germany
Author contributions: Schulz C and Stemmler HJ contributed equally to this work; Heinemann V and Schalhorn A designed the study; Moosmann N, Boeck S and Giessen C were involved in editing the manuscript; Heinemann V co-ordinated the data collection and its interpretation; Zwingers T provided the statistical analysis; Schulz C and Stemmler HJ analyzed data and wrote the paper.
Correspondence to: Priv.-Doz. Dr. Hans-Joachim Stemmler, Department of Haematology & Oncology, Ludwig-Maximilians University of Munich, Campus Grosshadern, Marchioninistr 15, Munich 81377, Germany. joachim.stemmler@med.uni-muenchen.de
Telephone: +49-89-70956017 Fax: +49-89-70958897
Received: March 26, 2009
Revised: September 27, 2009
Accepted: October 4, 2009
Published online: October 28, 2009
Abstract

AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen.

METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC.

RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the (6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P = 0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P =0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].

CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.

Keywords: Irinotecan; Colorectal cancer; UGT1A1; Gene polymorphism; Toxicity; Efficacy; Delayed diarrhoea; Neutropenia