NDLI: Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers

Content Provider	PubMed Central
Author	Moriya, Hiroyuki Saito, Katsuhiko Helsby, Nuala Sugino, Shigekazu Yamakage, Michiaki Sawaguchi, Takeru Takasaki, Masahiko Kato, Hidenori Kurosawa, Nahoko
Copyright Year	2014
Abstract	The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is associated with the 6 and 28 alleles of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). However, the correlation between these variants and the occurrence of severe neutropenia in a low-dose CPT-11 regimen for the treatment of gynecological cancers has not been extensively studied. There are also no studies regarding the association between the 421C>A mutation in ATP-binding cassette sub-family G member 2 (ABCG2) and the occurrence of severe neutropenia in CPT-11-treated patients with gynecological cancers. The present study was designed to determine the factors associated with the occurrence of grade 4 neutropenia during chemotherapy for gynecological cancers with combinations of CPT-11 and cisplatin or mitomycin C. In total, 44 patients with gynecological cancer were enrolled in the study. The association between the absolute neutrophil count (ANC) nadir values, the total dose of CPT-11 and the genotypes of UGT1A1 or ABCG2 was studied. No correlation was observed between the ANC nadir values and the total dose of CPT-11. The ANC nadir values in the UGT1A16/28 and 6/6 groups were significantly lower compared with those in the 1/1 group (P<0.01). Univariate analysis showed no association between the occurrence of grade 4 neutropenia and the ABCG2 421C>A mutation. Subsequent to narrowing the factors by univariate analysis, multivariate logistic regression analysis only detected significant correlations between the occurrence of grade 4 neutropenia and the UGT1A16/6 and 6/28 groups (P=0.029; odds ratio, 6.90; 95% confidence interval, 1.22–38.99). No associations were detected between the occurrence of grade 4 neutropenia and the heterozygous variant (1/6 or 1/28) genotype, type of regimen or age. In conclusion, the UGT1A16/28 and 6/6 genotypes were found to be associated with the occurrence of severe neutropenia in the low-dose CPT-11 regimen for gynecological cancers. This finding indicates that the determination of UGT1A1 variants may be as useful in CPT-11 chemotherapy for gynecological conditions as it is in colorectal and lung cancer patients treated with this drug.
Related Links	http://dx.doi.org/10.3892/ol.2014.2046
Starting Page	2035
File Format	PDF
ISSN	17921074
e-ISSN	17921082
Journal	Oncology Letters
Issue Number	6
Volume Number	7
Language	English
Publisher	D.A. Spandidos
Publisher Date	2014-04-01
Access Restriction	Open
Rights Holder	D.A. Spandidos
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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