title: Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer.
abstract: Hepatotoxicity is a major cause of the withdrawal of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) when treating EGFR mutation-positive non-small cell lung cancer (NSCLC). We report a case in which gefitinib- and elrotinib-induced severe hepatotoxicity arose in a patient with the uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1) and cytochrome p450 3A5 (CYP3A5) poor metabolizer phenotypes. Afatinib is not significantly metabolized by cytochrome p450-mediated pathways. We describe successful management of the patient's tumor by switching to afatinib. Evaluation of single nucleotide polymorphisms (SNPs) in metabolic enzymes might be useful to predict severe hepatotoxicity induced by EGFR-TKIs.
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Yoshitaka
authors: Y
authors: Zenke
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: sumemura@east.ncc.go.jp.
authors: Shigeki
authors: S
authors: Umemura
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Eri
authors: E
authors: Sugiyama
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Keisuke
authors: K
authors: Kirita
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Shingo
authors: S
authors: Matsumoto
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Kiyotaka
authors: K
authors: Yoh
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Seiji
authors: S
authors: Niho
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Hironobu
authors: H
authors: Ohmatsu
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors: Koichi
authors: K
authors: Goto
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants / Q000187:drug effects / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D019233:Retreatment; D016896:Treatment Outcome; D000099148:UGT1A1 Enzyme
chemical_list: D000970:Antineoplastic Agents; D051544:Cytochrome P-450 CYP3A; D066246:ErbB Receptors; D000077156:Gefitinib; D014453:Glucuronosyltransferase; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000099148:UGT1A1 Enzyme
keywords: Drug-related side effects and adverse reactions; EGFR genes; Lung cancer; Protein kinase inhibitors; Single nucleotide polymorphism