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Original Research

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UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama tumor board study

  • M. Takano1,*,
  • T. Goto1
  • J. Hirata1
  • K. Furuya1
  • K. Horie2
  • M. Takahashi2
  • H. Yokota2
  • N. Kino2
  • K. Kudoh3
  • Y. Kikuchi4

1Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa

2Department of Gynecology, Saitama Cancer Center, Adachi-gun

3Department of Obstetrics and Gynecology, Nishisaitama Chuo National Hospital, Tokorozawa

4Department of Gynecology, Ohki Memorial Kikuchi Cancer Clinic for Women, Tokorozawa, (Japan)

DOI: 10.12892/ejgo340202 Vol.34,Issue 2,March 2013 pp.120-123

Published: 24 March 2013

*Corresponding Author(s): M. Takano E-mail: mastkn@ndmc.ac.jp

Abstract

Introduction: Genotyping of UGT1A1 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 UGT1A1*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 UGT1A1 genotype. Results: Patients with homotype UGT1A1 alleles had a significantly lower glucuronidation ratio in comparison with UGT1A1 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.

Keywords

UDP-glucuronosyltransferase 1A1 (UGT1A1); UGT1A1*6; UGT1A1*28; Irinotecan; Cisplatin; Phase I.

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M. Takano,T. Goto,J. Hirata,K. Furuya,K. Horie,M. Takahashi,H. Yokota,N. Kino,K. Kudoh, Y. Kikuchi. UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama tumor board study. European Journal of Gynaecological Oncology. 2013. 34(2);120-123.

References

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