Successful treatment with afatinib after gefitinib- and erlotinib-induced hepatotoxicity.

Abstract

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.

• Authors: Hiroto Ueda, Hidetoshi Hayashi, Keita Kudo, Masayuki Takeda, Kazuhiko Nakagawa
• Journal: Investigational new drugs (Invest New Drugs) Vol. 34 Issue 6 Pg. 797-799 (12 2016) ISSN: 1573-0646 [Electronic] United States
• PMID: 27550238 (Publication Type: Case Reports, Journal Article)

Chemical References

• Quinazolines
• Radiation-Sensitizing Agents
• Afatinib
• Erlotinib Hydrochloride
• Gefitinib

Topics

• Adenocarcinoma (drug therapy)
• Afatinib
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Chemical and Drug Induced Liver Injury (drug therapy, etiology)
• Erlotinib Hydrochloride (administration & dosage)
• Female
• Gefitinib
• Humans
• Lung Neoplasms (drug therapy)
• Prognosis
• Quinazolines (administration & dosage, therapeutic use)
• Radiation-Sensitizing Agents (therapeutic use)