Abstract | INTRODUCTION: 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.
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Authors | M Takano, T Goto, J Hirata, K Furuya, K Horie, M Takahashi, H Yokota, N Kino, K Kudoh, Y Kikuchi |
Journal | European journal of gynaecological oncology
(Eur J Gynaecol Oncol)
Vol. 34
Issue 2
Pg. 120-3
( 2013)
ISSN: 0392-2936 [Print] Singapore |
PMID | 23781580
(Publication Type: Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Irinotecan
- UGT1A1 enzyme
- Glucuronosyltransferase
- Cisplatin
- Camptothecin
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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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