title: Study of efficacy and safety of pulsatile administration of high-dose gefitinib or erlotinib for advanced non-small cell lung cancer patients with secondary drug resistance: A single center, single arm, phase II clinical trial.
abstract: BACKGROUND
  The objective of the study was to observe the efficacy and safety of pulsatile administration of high-dose gefitinib or erlotinib in patients with advanced non-small cell lung cancer (NSCLC) with secondary drug resistance to standard doses of tyrosine kinase inhibitor (TKI) treatment.
  
  
  METHODS
  We recruited 42 NSCLC patients from our hospital, between August 2014 and December 2015, who had experienced drug resistance after one year of conventional treatment with gefitinib or erlotinib. The gefitinib group (29 patients) received one dose of 1000 mg gefitinib every four days. The erlotinib group (13 patients) received one dose of 450 mg erlotinib every three days. Treatments continued until disease progression according to Response Evaluation Criteria In Solid Tumors 1.1 or development of intolerable toxicity.
  
  
  RESULTS
  Median progression-free survival (PFS) was 30 months (gefitinib vs. erlotinib: 31 vs. 24 months; P > 0.05). After high-dose pulsatile administration, eight patients achieved a partial response (PR), 11 had stable disease (SD), and 23 had progressive disease (PD; relative risk 19.0%; disease control rate 45.2%; median PFS six months). Patients were categorized based on epidermal growth factor receptor gene mutation: exon 19 (no patients achieved complete response [CR], 4 PR, 6 SD, and 17 PD) and exon 21 mutation groups (no patients achieved CR, 4 PR, 5 SD, and 6 PD).
  
  
  CONCLUSIONS
  High-dose TKI pulsatile treatment is safe, efficient, and can improve prognoses for certain patients with advanced NSCLC.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yanzhe
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Tai
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Oncology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China. yueyinpan1965@126.com.
authors.forename: Yueyin
authors.initials: Y
authors.lastname: Pan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: 
  Drug resistance; erlotinib; gefitinib; pulsatile administration