title: Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer.
abstract: OBJECTIVE
  To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity, and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS).
  
  
  RESULTS
  Median gross tumor volume, mean lung dose, and lung V20 were 56 cm(3), 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively.
  
  
  CONCLUSIONS
  Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally advanced or metastatic NSCLC.
authors.affiliation: Army Radiation Cancer Center and Department of Radiation Oncology, Air Force General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ting-Yi
authors.initials: TY
authors.lastname: Xia
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Hong-Qi
authors.initials: HQ
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Wang
authors.forename: Dong-Shu
authors.initials: DS
authors.lastname: Chang
authors.forename: Liy-Yuan
authors.initials: LY
authors.lastname: Liu
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Di
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Wei-Zhang
authors.initials: WZ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011799:Quinazolines / Q000627:therapeutic use; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib