title: Phase II trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer.
abstract: OBJECTIVE
  Brain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety.
  
  
  METHODS
  Eligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility.
  
  
  RESULTS
  Forty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n = 36). No increase in neurotoxicity was detected, and no patient experienced grade ≥ 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations.
  
  
  CONCLUSIONS
  Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.
authors: Department of Radiation Oncology, Unit 97, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. jwelsh@mdanderson.org
authors: James W
authors: JW
authors: Welsh
authors: Ritsuko
authors: R
authors: Komaki
authors: Arya
authors: A
authors: Amini
authors: Mark F
authors: MF
authors: Munsell
authors: Wyatt
authors: W
authors: Unger
authors: Pamela K
authors: PK
authors: Allen
authors: Joe Y
authors: JY
authors: Chang
authors: Jeffrey S
authors: JS
authors: Wefel
authors: Susan L
authors: SL
authors: McGovern
authors: Linda L
authors: LL
authors: Garland
authors: Su S
authors: SS
authors: Chen
authors: Jamie
authors: J
authors: Holt
authors: Zhongxing
authors: Z
authors: Liao
authors: Paul
authors: P
authors: Brown
authors: Erik
authors: E
authors: Sulman
authors: John V
authors: JV
authors: Heymach
authors: Edward S
authors: ES
authors: Kim
authors: Baldassarre
authors: B
authors: Stea
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary* / Q000628:therapy*; D059248:Chemoradiotherapy; D016371:Cranial Irradiation; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors