Association Between the Low-dose Irinotecan Regimen-induced Occurrence of Grade 4 Neutropenia and Genetic Variants of in Patients with Gynecological Cancers

Overview

Journal Oncol Lett

Specialty Oncology

Date 2014 Jun 17

PMID 24932285

Citations 4

Authors

Hiroyuki Moriya

Katsuhiko Saito

Nuala Helsby

Shigekazu Sugino

Michiaki Yamakage

Takeru Sawaguchi

Masahiko Takasaki

Hidenori Kato

Nahoko Kurosawa

Affiliations

Soon will be listed here.

Abstract

The occurrence of severe neutropenia during treatment with irinotecan (CPT-11) is associated with the and alleles of uridine diphosphate glucuronosyltransferase 1A1 (). 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 () 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 or was studied. No correlation was observed between the ANC nadir values and the total dose of CPT-11. The ANC nadir values in the and groups were significantly lower compared with those in the group (P<0.01). Univariate analysis showed no association between the occurrence of grade 4 neutropenia and the 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 and 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 ( or ) genotype, type of regimen or age. In conclusion, the and 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 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.

Citing Articles

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Effect of drug metabolizing enzymes and transporters in Thai colorectal cancer patients treated with irinotecan-based chemotherapy.

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Correlation between UGT1A1 gene polymorphism and irinotecan chemotherapy in metastatic colorectal cancer: a study from Guangxi Zhuang.

Chen S, Hua L, Feng C, Mo Q, Wei M, Shen Y BMC Gastroenterol. 2020; 20(1):96.

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