title: Erlotinib in combination with pemetrexed/cisplatin for leptomeningeal metastases and cerebrospinal fluid drug concentrations in lung adenocarcinoma patients after gefitinib faliure.
abstract: Limited treatment options are available for lung cancer with brain metastases. Recent reports indicated that erlotinib and pemetrexed had synergistic effects in lung adenocarcinoma. Thus, we speculated that erlotinib plus pemetrexed/cisplatin may be more effective for the treatment of refractory central nervous system metastases in patients after gefitinib failure. Six lung adenocarcinoma patients with leptomeningeal metastasis (LM) who showed initial good response to gefitinib and subsequent gefitinib resistance were enrolled in this retrospective study. Five of the six patients had an epidermal growth factor receptor (EGFR) mutation in the primary tumor tissues or plasma. One patient showed complete remission, two patients showed a partial response, and two patients had stable disease. Performance and symptoms improved in the six patients. The survival time after the combination therapy was from 8 to 15 months (median, 9 months). There was no significant difference in cerebrospinal fluid (CSF) penetration rates of erlotinib between the erlotinib-only and the combination groups (P = 0.44). Erlotinib combined with pemetrexed/cisplatin may be effective in the treatment of LM in EGFR mutation patients after gefitinib failure. Small but measurable penetration of erlotinib and pemetrexed into the CSF was observed.
authors.affiliation: Department of Respiratory Oncology, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, 510120, Guangzhou, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Yang
authors.forename: Xinyun
authors.initials: X
authors.lastname: Yang
authors.forename: Yalei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Deng
authors.forename: Meiling
authors.initials: M
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002853:Chromatography, Liquid; D002945:Cisplatin / Q000008:administration & dosage / Q000134:cerebrospinal fluid; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000134:cerebrospinal fluid; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D055756:Meningeal Carcinomatosis / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed / Q000008:administration & dosage / Q000134:cerebrospinal fluid; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D053719:Tandem Mass Spectrometry
chemical_list: D011799:Quinazolines; D000068437:Pemetrexed; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin; D000077156:Gefitinib