Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer

Yoshitaka Zenke; Shigeki Umemura; Eri Sugiyama; Keisuke Kirita; Shingo Matsumoto; Kiyotaka Yoh; Seiji Niho; Hironobu Ohmatsu; Koichi Goto

doi:10.1016/j.lungcan.2016.05.002

Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer

Lung Cancer. 2016 Sep:99:1-3. doi: 10.1016/j.lungcan.2016.05.002. Epub 2016 Jun 6.

Authors

Yoshitaka Zenke¹, Shigeki Umemura², Eri Sugiyama¹, Keisuke Kirita¹, Shingo Matsumoto¹, Kiyotaka Yoh¹, Seiji Niho¹, Hironobu Ohmatsu¹, Koichi Goto¹

Affiliations

¹ Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
² Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. Electronic address: sumemura@east.ncc.go.jp.

PMID: 27565905
DOI: 10.1016/j.lungcan.2016.05.002

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.

Keywords: Drug-related side effects and adverse reactions; EGFR genes; Lung cancer; Protein kinase inhibitors; Single nucleotide polymorphism.

Publication types

Case Reports

MeSH terms

Antineoplastic Agents / administration & dosage
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Non-Small-Cell Lung / diagnosis
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics*
Chemical and Drug Induced Liver Injury
Cytochrome P-450 CYP3A / genetics
Cytochrome P-450 CYP3A / metabolism
ErbB Receptors / genetics*
Gefitinib
Glucuronosyltransferase / genetics
Glucuronosyltransferase / metabolism
Humans
Lung Neoplasms / diagnosis
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics*
Middle Aged
Mutation*
Pharmacogenetics
Pharmacogenomic Variants / drug effects
Pharmacogenomic Variants / genetics
Polymorphism, Single Nucleotide
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / therapeutic use*
Quinazolines / administration & dosage
Quinazolines / therapeutic use*
Retreatment
Treatment Outcome

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Quinazolines
Cytochrome P-450 CYP3A
UGT1A1 enzyme
Glucuronosyltransferase
ErbB Receptors
Gefitinib