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High total bilirubin level is a significant risk factor for severe neutropenia in patients receiving irinotecan-based chemotherapy

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Abstract

Irinotecan is effective for the treatment of metastatic colorectal cancer (mCRC) and advanced pancreatic cancer (aPC). However, these treatments are often limited due to the incidence of severe neutropenia. We identified risk factors for severe neutropenia in patients with mCRC or aPC, receiving irinotecan-based chemotherapy regimens. The study selected 104 patients (mCRC: 53 and aPC: 51) who received irinotecan-based chemotherapy between January 2014 and May 2018 and who were included in the present study. The initial dose of irinotecan was 150 mg/m2 in all patients, and patients with a lower initial dose of irinotecan were excluded. Severe neutropenia (grade ≥ 3) occurred in 56 patients (53.8%). Multivariable Cox proportional hazards analysis indicated that modified FOLFIRINOX (mFOLFIRINOX) and serum total bilirubin (T-Bil) were significant risk factors for severe neutropenia. Moreover, with receiver-operating characteristic (ROC) curve analysis, the cutoff for T-Bil was found to be 0.7 mg/dL. Among patients treated with mFOLFIRINOX therapy, the incidence of severe neutropenia was significantly higher in patients with high level of T-Bil (> 0.7 mg/dL) than in those without it (93.8% vs 55.0%, P = 0.006). A chemotherapy regimen (modified FOLFIRINOX therapy) and T-Bil > 0.7 mg/dL were significant risk factors for severe neutropenia in patients receiving 150 mg/m2 irinotecan.

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Funding

This study did not receive funding from any funding source.

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Authors and Affiliations

  1. Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan

    Yunami Yamada, Hironori Fujii, Koichi Ohata, Hiroko Kato-Hayashi, Daichi Watanabe & Akio Suzuki

  2. Gifu University Hospital Innovative and Clinical Research Promotion Center Gifu University, Gifu, 501-1194, Japan

    Takuma Ishihara

  3. First Department of Internal Medicine, Gifu University Hospital, Gifu, 501-1194, Japan

    Shinya Uemura, Takuji Iwashita & Masahito Shimizu

  4. Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, 501-1193, Japan

    Hisashi Imai, Nobuhisa Matsuhashi, Takao Takahashi & Kazuhiro Yoshida

  5. Laboratory of Pharmacy Practice and Social Science, Gifu Pharmaceutical University, Gifu, 501-1196, Japan

    Tadashi Sugiyama

Authors
  1. Yunami Yamada
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  2. Hironori Fujii
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  3. Koichi Ohata
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  4. Hiroko Kato-Hayashi
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  14. Kazuhiro Yoshida
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  15. Akio Suzuki
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Corresponding author

Correspondence to Hironori Fujii.

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Conflict of interest

K Yoshida received grants, personal fees, and nonfinancial support from Chugai Pharmaceutical Co., Ltd. during the conduct of this study; grants and personal fees from Taiho Pharmaceutical Co., Ltd., Pfizer Inc., and Yakult Honsha Co., Ltd.; and grants from Bristol-Myers Squibb and Kyowa Hakko Kirin Co., Ltd. outside the submitted work. He also received honoraria from Taiho Pharmaceutical Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., and Yakult Honsha Co., Ltd., and had a consultant or advisory relationship with Taiho Pharmaceutical Co., Ltd. and La Roche, Ltd. T. Takahashi has received honoraria for lectures from Takeda Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to disclose.

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Yamada, Y., Fujii, H., Ohata, K. et al. High total bilirubin level is a significant risk factor for severe neutropenia in patients receiving irinotecan-based chemotherapy. Med Oncol 36, 63 (2019). https://doi.org/10.1007/s12032-019-1288-7

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  • DOI: https://doi.org/10.1007/s12032-019-1288-7

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