title: UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama Tumor Board study.
abstract: BACKGROUND
  Genotyping of UGTI1Al could be useful for prediction of severe toxicities for patients treated with irinotecan; however, genotype-based recommended dose (RD) has not been established. The aim of the present study was to determine the RD of irinotecan in combination with cisplatin (CPT-P) for individuals with or without UGT1A1 polymorphisms.
  
  
  METHODS
  According to polymorphisms of UGTIAl*28, *6, and *27, RDs were determined by three-case cohort methods for patients with wild-type and heterotype, and by inter-patient dose escalation for homotype patients. Pharmacokinetic studies were also evaluated. During May 2009 and July 2011, 18 Japanese patients were enrolled; 16 patients with ovarian carcinoma, and two cases with cervical cancer. The RD of irinotecan was determined as 50 mg/m2 for the patients with wild-type, 40 mg/m2 for those with heterotype, and 30 mg/m2 for homotype UGT IAl genotype.
  
  
  RESULTS
  Patients with homotype UGTIAl1 alleles had a significantly lower glucuronidation ratio in comparison with UGTIAI wild-type and heterotype cases.
  
  
  CONCLUSIONS
  UGT1A1 genotype-based RDs of irinotecan in CPT-P therapy were determined. Further studies to investigate efficacy of the RD including response evaluation are needed to confirm the present results.
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Japan. mastkn@ndmc.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takano
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: J
authors.initials: J
authors.lastname: Hirata
authors.forename: K
authors.initials: K
authors.lastname: Furuya
authors.forename: K
authors.initials: K
authors.lastname: Horie
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Yokota
authors.forename: N
authors.initials: N
authors.lastname: Kino
authors.forename: K
authors.initials: K
authors.lastname: Kudoh
authors.forename: Y
authors.initials: Y
authors.lastname: Kikuchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / 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; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D002945:Cisplatin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme