Erlotinib Versus Gefitinib for Control of Leptomeningeal Carcinomatosis in Non-Small-Cell Lung Cancer

Introduction: Leptomeningeal carcinomatosis (LMC) from non-small-cell lung cancer (NSCLC) is a clinically important neurological complication in the era of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The purpose of this study was to compare the efficacy of gefitinib and erlotinib for control of LMC in NSCLC. Methods: We retrospectively reviewed medical records of 25 EGFR TKI-treated NSCLC patients with LMC between 2004 and 2012 at Seoul National University Hospital. Cytologic negative conversion was defined as absence of malignant cells in the cerebrospinal fluid three times in succession. Cytologic conversion rates were compared between the gefitinib arm and the erlotinib arm. Results: Nine patients had exon 21 point mutations and eight patients had exon 19 deletional mutations. Nine of 25 patients had already used EGFR TKIs and switched to another EGFR TKI after LMC occurrence. The other 16 patients received EGFR TKIs after LMC diagnoses. All the patients received intrathecal chemotherapy, including methotrexate, and six of them were treated with combined whole-brain radiotherapy. Gefitinib and erlotinib were administered to 11 and 14 patients, respectively. Ten patients had LMC controlled with cytologic negative conversion, whereas in 15 patients, cytological clearance of the cerebrospinal fluid could not be achieved. Patients treated with erlotinib showed better cytologic conversion rate of LMC than those with gefitinib (64.3% [9 of 14] in the erlotinib arm versus 9.1% [1 of 11] in the gefitinib arm; p = 0.012). Conclusion: This study suggested that erlotinib had better control rate for LMC in NSCLC than gefitinib. Further prospective study is warranted.