IMR Press / EJGO / Volume 34 / Issue 2 / pii/1630905776850-1377635579

European Journal of Gynaecological Oncology (EJGO) is published by IMR Press from Volume 40 Issue 1 (2019). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with S.O.G.

Original Research
UGT1A1 genotype-specific phase I and pharmacokinetic study for combination chemotherapy with irinotecan and cisplatin: a Saitama tumor board study
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1 Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa
2 Department of Gynecology, Saitama Cancer Center, Adachi-gun
3 Department of Obstetrics and Gynecology, Nishisaitama Chuo National Hospital, Tokorozawa
4 Department of Gynecology, Ohki Memorial Kikuchi Cancer Clinic for Women, Tokorozawa, (Japan)
Eur. J. Gynaecol. Oncol. 2013, 34(2), 120–123;
Published: 10 April 2013

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 2009and 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.
UDP-glucuronosyltransferase 1A1 (UGT1A1)
Phase I
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