Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer.
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.
Salgado
Josefa
J
Laboratory of Biotechnology, University Clinic of Navarra, 31008 Pamplona, Navarra, Spain. jsalgadog@unav.es
Zabalegui
Natalia
N
Gil
Carmen
C
Monreal
Ignacio
I
Rodríguez
Javier
J
García-Foncillas
Jesús
J
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D018450:Disease Progression; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017353:Gene Deletion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015233:Models, Statistical; D009154:Mutation; D011110:Polymorphism, Genetic; D011799:Quinazolines / Q000008:administration & dosage*; D017422:Sequence Analysis, DNA; D013876:Thiophenes / Q000008:administration & dosage*; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D013876:Thiophenes; D003841:Deoxycytidine; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; C068874:raltitrexed; D005472:Fluorouracil