Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer
Josefa Salgado (1), Natalia Zabalegui (4), Carmen Gil (1), Ignacio Monreal (2), Javier Rodríguez (3) and Jesús García-Foncillas (1,3)
Laboratories of (1) Biotechnology, (2) Biochemistry and (3) Department of Oncology, University Clinic of Navarra (CUN), Avda. Pio XII 36; 4Laboratory of Gene Therapy Application, Centre for Applied Medical Research (CIMA), Avda. Pio XII 55, 31008 Pamplona, Navarra, Spain
Magazine: Oncology Reports
Date: Feb 1, 2007Medical Oncology Biochemistry [SP] Clinical Genetics Unit [SP] Digestive Tract Tumours Area
Pharmacogenetics is an increasingly useful field where the genetic studies are becoming an important tool for predicting drug toxicity and/or efficacy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene polymorphisms could be highly informative tools in the clinical handling of colorectal cancer patients, who are following fluoropyrimidine based chemotherapy. Fifty-eight patients, with non-resectable metastatic colorectal cancer, were treated with capecitabine and raltitrexed, every three weeks.
Patients were divided in a good-response group (complete and partial response) and a poor-response group (stable and progression). A genotype panel TS-DPD was evaluated. Results show that TS genotype analysis clearly differentiates patients with a worst response to a 5-fluorouracil based chemotherapy. DPD genotype was shown to be highly informative for prediction of toxicity of the treatment.
These polymorphisms could represent an accurate, rapid and effective determination panel, indicative of resistance and toxicity for patients undergoing fluoropyrimidine based treatment.
CITATION Oncol Rep. 2007 Feb;17(2):325-8
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