Geoffrey Y Ku1, Akhil Chopra, Gilberto de Lima Lopes. 1. Johns Hopkins Singapore International Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States. geoffrey@imc.jhmi.edu
Abstract
INTRODUCTION: Hepatotoxicity secondary to gefitinib, an oral tyrosine kinase inhibitor (TKI) against the epidermal growth factor receptor (EGFR), is under-appreciated, even though it has a reported incidence of 10-20% in phase II trials. METHODS/ RESULTS: We present two patients with non-small cell lung cancer (NSCLC) who developed grade 2/3 hepatotoxicity starting between 4 and 6 weeks after initiation of gefitinib, with toxicity peaking between 10 and 20 weeks. Both patients were switched to treatment with erlotinib, another EGFR TKI, without further development of hepatotoxicity. One patient with measurable metastatic disease achieved a durable near complete response while on erlotinib. The other patient experienced recurrence of hepatotoxicity when gefitinib was briefly reintroduced. CONCLUSIONS: Patients with NSCLC receiving gefitinib should undergo routine monitoring of liver enzymes. For those who develop gefitinib-induced hepatotoxicity but are otherwise deriving clinical benefit, consideration can be given to switching to erlotinib.
INTRODUCTION:Hepatotoxicity secondary to gefitinib, an oral tyrosine kinase inhibitor (TKI) against the epidermal growth factor receptor (EGFR), is under-appreciated, even though it has a reported incidence of 10-20% in phase II trials. METHODS/ RESULTS: We present two patients with non-small cell lung cancer (NSCLC) who developed grade 2/3 hepatotoxicity starting between 4 and 6 weeks after initiation of gefitinib, with toxicity peaking between 10 and 20 weeks. Both patients were switched to treatment with erlotinib, another EGFR TKI, without further development of hepatotoxicity. One patient with measurable metastatic disease achieved a durable near complete response while on erlotinib. The other patient experienced recurrence of hepatotoxicity when gefitinib was briefly reintroduced. CONCLUSIONS:Patients with NSCLC receiving gefitinib should undergo routine monitoring of liver enzymes. For those who develop gefitinib-induced hepatotoxicity but are otherwise deriving clinical benefit, consideration can be given to switching to erlotinib.