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UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama Tumor Board study.

AbstractINTRODUCTION:
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.
MATERIALS AND 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.
CONCLUSION:
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.
AuthorsM Takano, T Goto, J Hirata, K Furuya, K Horie, M Takahashi, H Yokota, N Kino, K Kudoh, Y Kikuchi
JournalEuropean journal of gynaecological oncology (Eur J Gynaecol Oncol) Vol. 34 Issue 2 Pg. 120-3 ( 2013) ISSN: 0392-2936 [Print] Singapore
PMID23781580 (Publication Type: Clinical Trial, Phase I, Journal Article)
Chemical References
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Cisplatin
  • Camptothecin
Topics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Camptothecin (administration & dosage, analogs & derivatives)
  • Cisplatin (administration & dosage)
  • Female
  • Genotype
  • Glucuronosyltransferase (genetics)
  • Humans
  • Irinotecan
  • Middle Aged
  • Ovarian Neoplasms (drug therapy, genetics)

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