title: Activity of pemetrexed and high-dose gefitinib in an EGFR-mutated lung adenocarcinoma with brain and leptomeningeal metastasis after response to gefitinib.
abstract: About 20% to 40% of patients with non-small cell lung cancer (NSCLC) will develop brain metastases during the natural course of their disease. The prognosis for such patients is very poor with limited survival. In addition to the standard whole brain radiation therapy (WBRT), some studies have shown that chemotherapy drugs and/or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) can improve the outcome of these patients. Here, we report a stage IIIA patient who developed multiple brain metastases one year after operation. Oral gefitinib with concurrent WBRT were given as first-line therapy. Complete response and a 50-month progression-free survival (PFS) were obtained. Double dosage of gefitinib (500 mg per day) together with pemetrexed were given as the second-line therapy after the patient developed new brain lesions and leptomeningeal metastasis during the maintenance therapy of gefitinib. The PFS for the second-line therapy was six months. In total, the patient obtained an overall survival of 59 months since the first diagnosis of brain metastases. Mutational analysis showed a 15-nucleotide deletion and a missense mutation in exon 19 of the EGFR gene, and a missense mutation at codon 12 of the K-ras gene. These underlying genetic changes might partially explain the long-term survival of this patient after brain metastases when treated with concurrent or sequential therapies of EGFR-TKI, radiotherapy and chemotherapy.
authors.affiliation: Department of Medical Oncology, Second Affiliated Hospital Zhejiang University College of Medicine, 88, Jiefang Road, Hangzhou 310009, Zhejiang, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.forename: Chunwen
authors.initials: C
authors.lastname: Tan
authors.forename: Modan
authors.initials: M
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Fang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Hu
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary*; D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D008198:Lymph Nodes / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D055756:Meningeal Carcinomatosis / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D008875:Middle Aged; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011013:Pneumonectomy / Q000379:methods; D011799:Quinazolines / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D006147:Guanine; D066246:ErbB Receptors; D000077156:Gefitinib