Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib-Induced Hepatotoxicity: Review of 8 Clinical Cases

Objective. Gefitinib often induces liver damage. A few reports have described that the subsequent administration of erlotinib was associated with less hepatotoxicity, but the safety and efficacy of this treatment are still not fully investigated. Therefore, we evaluated retrospectively the patients with erlotinib following gefitinib-induced hepatotoxicity. Methods and Patients. We retrospectively reviewed the medical records between December 2007 and March 2010. The patients were evaluated including the following information: age, gender, histology of lung cancer, performance status, smoking status, epidermal growth factor receptor (EGFR) mutation status, liver metastasis, viral hepatitis, alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib following gefitinib-induced hepatotoxicity. All achieved disease control by gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively. The median duration of treatment with gefitinib was 112.5 days and the median time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions. Erlotinib administration with careful monitoring is thought to be a good alternative strategy for patients who respond well to gefitinib treatment but experience hepatotoxicity. 1. Introduction Lung cancer is the leading cause of cancer death worldwide. For patients with advanced non-small-cell lung cancer (NSCLC), systemic chemotherapy combined with platinum compound and a third-generation agent is considered as standard first-line treatment. On the other hand, gefitinib, one of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), is effective, especially in patients with adenocarcinomas who are women, never-smokers and Asian [1].Recently, several studies have shown that NSCLC tumors were highly responsive to the EGFR-TKIs, gefitinib and erlotinib, in patients with somatic mutations of the EGFR gene, such as a point mutation at exon 21 (L858R) or a base pair-deletion at exon 19 (del746_A750) [2–4]. Moreover, an improvement in progression free survival was also seen in NSCLC patients with an EGFR gene mutation who were treated with first-line gefitinib [5, 6]. However, various adverse events, such as skin rash and diarrhea, have been seen following gefitinib treatment and among them, hepatotoxicity is relatively underappreciated. Severely