Abstract
BackgroundErlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. Severe hepatotoxicity was observed in 4% to 31% of patients receiving erlotinib treatment prompting delay or termination of treatment. Only a few factors related to hepatotoxicity of erlotinib have been reported. No study has investigated the role of concomitant medications and erlotinib-induced hepatotoxicity. The aim of this study was to investigate the association between erlotinib-induced hepatotoxicity and various factors including concomitant medications in patients with NSCLC and pancreatic cancer.MethodsFrom January 2014 to June 2017, a retrospective study was conducted in patients with NSCLC and pancreatic cancer, who were treated with erlotinib. Various data were reviewed, including sex, age, body weight, height, body surface area (BSA), underlying disease, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), smoking history, erlotinib dose, EGFR mutation, and concomitant drugs.ResultsThe incidence of grade 2 or higher hepatotoxicity in the study group of patients was 17.2%. Multivariate analysis showed a 2.7-fold increase in hepatotoxicity with the concomitant use of CYP3A4 inducers. In NSCLC patients, co-administration of H2-antagonist/PPI increased hepatotoxicity 3.5-fold. Among the demographic factors, liver metastasis and age ≥ 65 years were significant risk factors in all study patients and NSCLC patients, respectively; the attributable risks for liver metastasis and age were 46.3% and 71.8%, respectively. Subgroup analysis using pancreatic cancer patients yielded marginally significant results with CYP3A4 inducers and erlotinib-induced hepatotoxicity. Liver metastasis and CYP3A4 inducers also shortened time to hepatotoxicity 2.1 and 2.3-fold, respectively.ConclusionsOur study showed that concomitant use of CYP3A4 inducers and H2-antagonist/PPI, liver metastasis, and age ≥ 65 were associated with erlotinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially in patients using CYP3A4 inducers and anti-acid secreting agents.
Highlights
Erlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer
The exclusion criteria were: patients who were not diagnosed with NSCLC or pancreatic cancer, had underlying liver diseases, an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level on day one of erlotinib administration, and lack of liver function test results
Diabetes mellitus (DM), pancreatic cancer, and liver metastasis were most frequently observed in patients with grade III and IV hepatotoxicity; while DM was a significant factor (AOR 2.3, 95% CI 1.0–5.1), the latter two were of marginal significance
Summary
Erlotinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. No study has investigated the role of concomitant medications and erlotinib-induced hepatotoxicity. The aim of this study was to investigate the association between erlotinib-induced hepatotoxicity and various factors including concomitant medications in patients with NSCLC and pancreatic cancer. The reported rates of incidence of lung cancer and pancreatic cancer in Korea are 11.1 and 2.7%, respectively. An EGFR tyrosine kinase inhibitor (TKI), is used for the treatment of non-small cell lung cancer (NSCLC) and pancreatic cancer. Studies showed that erlotinib improved progression-free survival compared with chemotherapy as a first-line treatment in Asian patients with NSCLC carrying activating EGFR mutations [5].
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