title: Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study.
abstract: BACKGROUND
  To investigate the effects of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28, *6 and *27 in patients with gynecologic cancer who received chemotherapy with irinotecan and cisplatin.
  
  
  METHODS
  Patients eligible for this study had cervical or ovarian cancer treated with chemotherapy; a course of the regimen consisted of 60 mg/m(2) of irinotecan on days 1, 8 and 15, and 60 mg/m(2) of cisplatin on day 1 every 4 weeks. UGT1A1 polymorphisms and toxicities were analyzed.
  
  
  RESULTS
  From March 2007 to December 2007, 30 Japanese patients were enrolled; 24 ovarian carcinoma patients and 6 cervical cancer patients. The following genotypes of UGT1A1 were found: wild type in 17 patients (57%), *28 in 4 patients (13%), *6 in 8 patients (27%), *28*6 in 1 case (3%) and no case of *27 (0%). Grade 3/4 neutropenia, thrombocytopenia and diarrhea were significantly more frequent in *6 patients compared with wild-type patients. Also, in *6 patients irinotecan administration on days 8 or 15 was significantly more often omitted due to toxicities. In patients with *28 or *28*6, side effects were similar to those in patients with *6.
  
  
  CONCLUSIONS
  In addition to UGT1A1*28, UGT1A1*6 might also be a key candidate to determine the dose of combination chemotherapy with irinotecan and cisplatin.
authors.affiliation: Department of Gynecology, Saitama Cancer Center, Adachi-Gun, Japan. mastkn@ndmc.ac.jp
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kato
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Junko
authors.initials: J
authors.lastname: Hirata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Furuya
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Harushige
authors.initials: H
authors.lastname: Yokota
authors.forename: Nao
authors.initials: N
authors.lastname: Kino
authors.forename: Koji
authors.initials: K
authors.lastname: Horie
authors.forename: Tomoko
authors.initials: T
authors.lastname: Goto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Kita
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D002945:Cisplatin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme