title: Severe irinotecan-induced toxicity in a patient with UGT1A1 28 and UGT1A1 6 polymorphisms.
abstract: Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing UGT1A1 28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1 28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UGT1A1 28 (TA 7/7), while UGT1A1 6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1 28 and UGT1A1 6 polymorphisms.
authors.affiliation: Affiliated Hospital Cancer Center, Academy of Military Medical Science, Beijing 100071, China. jmxu2003@yahoo.com
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Fei-Jiao
authors.initials: FJ
authors.lastname: Ge
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Ze-Yuan
authors.initials: ZY
authors.lastname: Liu
authors.forename: Manish R
authors.initials: MR
authors.lastname: Sharma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics; D003967:Diarrhea / Q000139:chemically induced* / Q000175:diagnosis; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009503:Neutropenia / Q000139:chemically induced* / Q000175:diagnosis; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D002955:Leucovorin; D000099148:UGT1A1 Enzyme
keywords: Irinotecan; Polymorphism; Toxicity; UGT1A1*28; UGT1A1*6