Successful treatment of two lung cancer patients with erlotinib following gefitinib-induced hepatotoxicity.
BACKGROUND
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.


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.
Ku
Geoffrey Y
GY
Johns Hopkins Singapore International Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States. geoffrey@imc.jhmi.edu
Chopra
Akhil
A
Lopes
Gilberto de Lima
Gde L
D000369:Aged, 80 and over; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018572:Disease-Free Survival; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity; D012008:Recurrence
D011799:Quinazolines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000069347:Erlotinib Hydrochloride; D001219:Aspartate Aminotransferases; D000077156:Gefitinib