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03.08.2020 | Original Article

ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy

verfasst von: Hisanaga Nomura, Daiki Tsuji, Ken Demachi, Nobuo Mochizuki, Haruki Matsuzawa, Tomonori Yano, Hiroyuki Daiko, Satoshi Fujii, Takashi Kojima, Kunihiko Itoh, Toshikatsu Kawasaki

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2020

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Abstract

Purpose

The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy.

Methods

A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression.

Results

A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008–1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002–1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087–4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108–4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors.

Conclusions

In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.

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Titel: ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy
verfasst von: Hisanaga Nomura
Daiki Tsuji
Ken Demachi
Nobuo Mochizuki
Haruki Matsuzawa
Tomonori Yano
Hiroyuki Daiko
Satoshi Fujii
Takashi Kojima
Kunihiko Itoh
Toshikatsu Kawasaki
Publikationsdatum: 03.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2020
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04118-9

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ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy