UGT1A1*28 and other UGT1A polymorphisms as determinants of irinotecan toxicity.
Irinotecan is a drug commonly used for the treatment of cancer patients, both as a single agent or in combination therapy. Neutropenia and diarrhea are the dose-limiting toxicities. Genetic variations of proteins involved in irinotecan metabolism and transport have been considered in the development of irinotecan toxicity. In particular, polymorphisms affecting UDP-glucuronosyltransferase isoform 1A1 (UGT1A1) expression or activity are being investigated. Among these, UGT1A1*28 has been considered as the major predictive pharmacogenetic marker for severe hematological toxicity (neutropenia). However, translation to clinical practice of UGT1A1*28 testing as a predictive marker of adverse effects needs to be further investigated and the available data are not conclusive in defining a precise genotype-based dosage. Further prospective studies are required to reach a personalization of chemotherapy with irinotecan.
Biason
P
P
Clinical and Experimental Pharmacology Division, CRO-Centro di Riferimento Oncologico, National Cancer Unstitute, Aviano, Italy.
Masier
S
S
Toffoli
G
G
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000494:pharmacology; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D011110:Polymorphism, Genetic; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme