Erlotinib Responds to Brain Metastasis of Lung Adenocarcinoma where Gefitinib Failed : A Case Report

Abstract

Gefitinib and erlotinib are small-molecule tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), and have an effect on advanced non-small-cell lung cancer (NSCLC) with mutated EGFR genes. We report the case of a patient with NSCLC harboring an EGFR mutation. His disease had remained stable on daily 250 mg of gefitinib for 13 months until brain metastases developed. After the discontinuation of gefitinib therapy, erlotinib was subsequently administered at a dose of 150 mg a day, which brought about marked shrinkage of the brain metastases while the other lesions remained stable.
Gefitinib is thought to poorly penetrate into the brain due to the presence of the blood-brain barrier. As a result, cancer cells in the brain might remain sensitive to EGFR-TKIs even if those in other lesions eventually acquire resistance to gefitinib. In contrast, erlotinib confers much higher serum concentrations than gefitinib because of the difference of dose setting. Thus, we speculate that erlotinib was able to cross the blood-brain barrier and elicited response on the brain metastases in this case.