Observation of hepatotoxicity during long-term gefitinib administration in patients with non-small-cell lung cancer

Abstract

To observe drug-induced hepatotoxicity by long-term gefitinib administration in the treatment of non-small-cell lung cancer. The data of 101 patients with locally advanced or metastatic non-small-cell lung cancer, for which gefitinib had been used orally for 3 months or longer, were retrospectively analyzed. The median duration of gefitinib administration was 14 months (3–60 months). Forty patients (39.6%) developed abnormal hepatic function, among whom 30 patients (29.7%) had grade I hepatotoxicity, six patients (5.9%) had grade II, and four patients (4.0%) had grade III, respectively. The median time from starting gefitinib oral therapy to developing liver dysfunction was 4 months (1–23 months) for the entire cohort. The incidence of hepatotoxicity in the group with a duration of more than 14 months was much higher than that in the group with a duration of less than 14 months (52.0 vs. 27.5%, P=0.012). In thirty-two patients (32/40), abnormal liver function resolved with hepatoprotective treatment, whereas eight patients (8/40) had persistent grade I hepatotoxicity until the last follow-up. Our study showed that long-term gefitinib-induced hepatotoxicity was a common adverse event, especially for the cohort with a duration of longer than 14 months. In most patients with hepatotoxicity, normal liver function was restored and discontinuation of gefitinib was not necessary.

Fluorescent Dye Labeling Changes the Biodistribution of Tumor-Targeted Nanoparticles

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Polychlorinated biphenyls disrupt hepatic epidermal growth factor receptor signaling

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GSK-3β regulates the endothelial-to-mesenchymal transition via reciprocal crosstalk between NSCLC cells and HUVECs in multicellular tumor spheroid models

“…Recently, there are several reports that hepatotoxicity were observed during long-term Gefitinib administration in patients with non-small-cell lung cancer [32–35]. Because we observed sudden death of mice during the administration of Gefitinib, we evaluated serum alanine aminotransferase (ALT) activity and aspartate aminotransferase (AST) values for hepatotoxicity assessment of experiment object mice in Fig.…”