title: Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage IIIA-N2 non-small cell lung cancer harbouring EGFR mutations: a randomized, phase II study.
abstract: BACKGROUND
  Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show great efficacy in patients with advanced non-small cell lung cancer (NSCLC) with EGFR mutations. The efficacy and safety of gefitinib following adjuvant chemotherapy in patients with EGFR mutation are unknown.
  
  
  METHODS
  In this open-label, phase II study, patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations (either exon 19 deletion or L858R point mutation) were assigned randomly to receive pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5), administered every 21 days for 4 cycles, followed with or without gefitinib (250 mg/day) for 6 months. The primary end point was disease-free survival (DFS).
  
  
  RESULTS
  From August 2008 to September 2011, 60 patients were included in our center. DFS was significantly longer among those who received pemetrexed and carboplatin (PC)-gefitinib than among those who received PC alone [hazard ratio (HR), 0.37; 95 % confidence interval (CI) 0.16-0.85; P = 0.014; median, 39.8 vs. 27.0 months]. The rates of 2-year DFS were 78.9 % in the PC-gefitinib group and 54.2 % in the PC alone group. The rates of 2-year overall survival (OS) were 92.4 % in the PC-gefitinib group and 77.4 % in the PC alone group (HR, 0.37; 95 % CI 0.12-1.11, P = 0.076). The most common adverse event was rash (43.3 %, 13/30) in the PC-gefitinib group and the administration of gefitinib following chemotherapy was well tolerated.
  
  
  CONCLUSIONS
  The administration of gefitinib following PC adjuvant therapy shows significant improvement in DFS in patients with resected stage IIIA-N2 NSCLC harbouring EGFR mutations.
authors.affiliation: Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ou
authors.forename: Xiong
authors.initials: X
authors.lastname: Ye
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Sun
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.forename: Song-Liang
authors.initials: SL
authors.lastname: Zhang
authors.forename: Bao-Xiao
authors.initials: BX
authors.lastname: Wang
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000556:secondary / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011013:Pneumonectomy; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; D066246:ErbB Receptors; D000077156:Gefitinib