Summary
Clinical trials of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib have shown that some patients receiving these agents develop severe hepatotoxicity that necessitates treatment cessation. Both drugs undergo extensive hepatic metabolism mediated predominantly by cytochrome P450 family enzymes. Afatinib is a second-generation, irreversible EGFR-TKI that competes with ATP for binding to EGFR and the related proteins HER2 and HER4 and whose major circulating metabolites are covalent drug-protein adducts. We here describe a patient with EGFR mutation–positive lung adenocarcinoma who developed severe hepatotoxicity during treatment first with gefitinib and then with erlotinib, but who was subsequently able to continue treatment with afatinib for at least 44 weeks with no evidence of hepatotoxicity or disease progression. As far as we are aware, this is the first report of successful treatment with afatinib after the development of high-grade hepatotoxicity during both gefitinib and erlotinib therapy.
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HH has received lecture fees from AstraZeneca K.K. and Chugai Pharmaceutical Co. Ltd. as well as advisory fees from AstraZeneca K.K. and Boehringer Ingelheim Japan Inc. KN has received lecture fees and advisory fees from Chugai Pharmaceutical Co. Ltd., AstraZeneca K.K., and Boehringer Ingelheim Japan Inc.
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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.
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Ueda, H., Hayashi, H., Kudo, K. et al. Successful treatment with afatinib after gefitinib- and erlotinib-induced hepatotoxicity. Invest New Drugs 34, 797–799 (2016). https://doi.org/10.1007/s10637-016-0384-1
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DOI: https://doi.org/10.1007/s10637-016-0384-1