A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression
| Autor: | A. Marquez, I. Sevilla, R. Duenas, P. Sanchez-Rovira, E. Alba, F. Carabantes, J. Lopez-Siles, E. Gonzalez, M. J. Sanchez, N. Ribelles, Ana I. Sánchez |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Antimetabolites Antineoplastic Genotype Colorectal cancer Clinical Biochemistry Breast Neoplasms Pilot Projects Thymidylate synthase Gastroenterology Deoxycytidine Carboxylesterase Capecitabine Predictive Value of Tests Internal medicine medicine Dihydropyrimidine dehydrogenase Humans Thymidine phosphorylase Dihydrouracil Dehydrogenase (NADP) Pharmacology Polymorphism Genetic biology business.industry Reverse Transcriptase Polymerase Chain Reaction DNA Neoplasm Thymidylate Synthase medicine.disease Endocrinology Fluorouracil Multivariate Analysis biology.protein Disease Progression Female Gene polymorphism business Colorectal Neoplasms medicine.drug |
| Zdroj: | Current drug metabolism. 9(4) |
| ISSN: | 1389-2002 |
| Popis: | Capecitabine is a drug that requires the consecutive action of three enzymes: carboxylesterase 2 (CES 2), cytidine deaminase (CDD), and thymidine phosphorylase (TP) for transformation into 5-fluorouracil (5FU). The metabolism of 5FU requires the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) among other enzymes. The present study prospectively examined the possible relationship between the toxicity and efficacy of capecitabine and 14 different polymorphisms in CES 2, CDD, TS and DPD. Between 2003 and 2005, a total of 136 patients with advanced breast or colorectal cancer treated with capecitabine were prospectively enrolled. The presence of two polymorphisms (CDD 943insC and CES 2 Exon3 6046 G/A) were associated with a non-statistically significant higher incidence of grade 3 hand-foot syndrome (HFS) (p=0.07) and grade 3-4 diarrhoea (p=0.09), respectively. Patients heterozygous or homozygous for the polymorphism CES 2 5'UTR 823 C/G exhibited a significantly greater response rate to capecitabine, and time to progression of disease (59%, 8.7 months) than patients with the wild type gene sequence (32%, p=0.015; 5.3 months, p=0.014). For the first time, an association between a polymorphism in the CES2 gene and the efficacy of capecitabine has been described, providing preliminary evidence of its predictive and prognostic value. |
| Databáze: | OpenAIRE |
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