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Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer

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Abstract

Background

The association between UGT1A1 polymorphism and etoposide-induced toxicities is still not clear. The aim of this study was to assess the association between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and severe hematologic toxicities in Japanese patients receiving etoposide plus platinum chemotherapy for small-cell lung cancer.

Methods

This retrospective analysis included patients with small-cell lung cancer who had received their first-line chemotherapy with etoposide plus cisplatin or carboplatin, between October 2008 and April 2018, at the University of Fukui Hospital. The relationship between UGT1A1 polymorphisms and first-cycle neutropenia as well as thrombocytopenia was evaluated.

Results

A total of 55 patients were enrolled. The incidence of grade 4 neutropenia during the first cycle of etoposide-based chemotherapy was higher in patients with homozygous (hmz) polymorphisms for UGT1A1*28 and *6 (*28/*28, *6/*6, and *6/*28) than in patients with wild-type (wt) (*1/*1) and heterozygous (htz) (*1/*28 and *1/*6) polymorphisms (88% vs 43% P = 0.03). The incidence of febrile neutropenia and grade 4 thrombocytopenia, however, was not significantly different. Multivariate analysis suggested that grade 4 neutropenia associated significantly with an hmz UGT1A1 genotype [odds ratio (OR) 11.3; P = 0.04] and administration of granulocyte colony-stimulating factor (G-CSF) before the neutrophil counts dropped to < 500 cells/µL (OR; P = 0.01).

Conclusions

UGT1A1*28 and UGT1A1*6 mutations might be regarded as predictors for etoposide-induced grade 4 neutropenia.

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Acknowledgements

We would like to thank the participating patients for their contribution to this study. We would also like to thank Editage (http://www.editage.jp) for English language editing. The results in this manuscript have been partly presented at the 54th annual meeting of Japanese Society of Clinical Oncology, Oct. 21, 2016.

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Authors and Affiliations

  1. Department of Pharmacy, University of Fukui Hospital, 23-3 Matsuoka-shimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan

    Yutaka Negoro, Ryoichi Yano, Mari Yoshimura, Yoko Suehiro, Shinji Yamashita, Takaaki Kodawara, Kyohei Watanabe, Hitoshi Tsukamoto & Nobuyuki Goto

  2. Medical Research Support Center, University of Fukui Hospital, Yoshida-gun, Fukui, Japan

    Kyohei Watanabe

  3. Education and Research Center for Clinical Pharmacy, Osaka Pharmaceutical University, Takatsuki, Osaka, Japan

    Toshiaki Nakamura

  4. Third Department of Internal Medicine, University of Fukui Hospital, Yoshida-gun, Fukui, Japan

    Maiko Kadowaki, Miwa Morikawa, Yukihiro Umeda, Masaki Anzai & Tamotsu Ishizuka

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  1. Yutaka Negoro
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  2. Ryoichi Yano
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Correspondence to Yutaka Negoro.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

The need for informed consent was waived because of the retrospective nature of the study.

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Negoro, Y., Yano, R., Yoshimura, M. et al. Influence of UGT1A1 polymorphism on etoposide plus platinum-induced neutropenia in Japanese patients with small-cell lung cancer. Int J Clin Oncol 24, 256–261 (2019). https://doi.org/10.1007/s10147-018-1358-4

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  • DOI: https://doi.org/10.1007/s10147-018-1358-4

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