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Case series on the association between blood levels and side effects of afatinib maleate

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Abstract

Purpose

Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug.

Methods

The study subjects were patients who were administered AFA for non-small cell lung cancer. Of these subjects, six patients agreed to participate in the study. The starting dose of AFA was 40 mg/day. We measured trough blood AFA levels on day 1 and 3 after AFA administration, on day 8–12, and every month until AFA administration was discontinued. Side effects were evaluated according to the adverse event codialect standard (CTCAE v.4.0).

Results

A temporary discontinuation and/or reduction in AFA dose (within 2 months) because of diarrhea and stomatitis was needed in four patients. Mean blood AFA levels on day 8–12 in these four patients were significantly higher than in other patients (47.0 ± 9.5 vs. 24.4 ± 0.1 ng/mL, P = 0.017). In addition, mean renal function prior to AFA administration in these four patients was significantly lower than that in the other patients (49.0 ± 9.6 mL/min/1.73 m2 vs. 77.2 ± 9.0, P = 0.026).

Conclusions

High blood AFA levels were associated with the early discontinuation and/or dose reduction of AFA because of untoward side effects, which may also be associated with decreased renal function.

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Acknowledgements

We were grateful to the Shimadzu Techno-Research, Inc., that measured AFA. This study was funded by research Grant of Iwate Medical University.

Author information

Author notes

  1. Junya Sato

    Present address: Department of Pharmacy, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

  2. Junya Sato and Naoto Morikawa contributed equally.

Authors and Affiliations

  1. Department of Pharmacy, Iwate Medical University Hospital, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan

    Junya Sato, Satoru Nihei & Kenzo Kudo

  2. Department of Clinical Pharmaceutics, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Shiwa-gun, Morioka-shi, Iwate, 028-3694, Japan

    Junya Sato, Satoru Nihei & Kenzo Kudo

  3. Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-shi, Iwate, 020-8505, Japan

    Naoto Morikawa, Ryosuke Chiba, Satoshi Moriguchi, Heisuke Saito & Kohei Yamauchi

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  1. Junya Sato
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  2. Naoto Morikawa
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Corresponding author

Correspondence to Junya Sato.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethical Review Board of the Iwate Medical University School of Medicine (H26-26). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Sato, J., Morikawa, N., Chiba, R. et al. Case series on the association between blood levels and side effects of afatinib maleate. Cancer Chemother Pharmacol 80, 545–553 (2017). https://doi.org/10.1007/s00280-017-3378-6

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  • DOI: https://doi.org/10.1007/s00280-017-3378-6

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