title: A front-line window of opportunity phase 2 study of sorafenib in patients with advanced nonsmall cell lung cancer: North Central Cancer Treatment Group Study N0326.
abstract: BACKGROUND
  The current study was conducted to assess the efficacy and toxicity of sorafenib as front-line therapy in patients with stage IIIB (pleural effusion) or IV nonsmall cell lung cancer (NSCLC).
  
  
  METHODS
  Patients received sorafenib 400 mg twice daily by mouth continuously, and were evaluated every 2 weeks during the first 8 weeks. Patients who manifested clinical progression during this period proceeded to receive standard of care. The primary endpoint was confirmed objective tumor response. A 2-stage Fleming design was used such that if at most 1 confirmed partial response (PR) or complete response was observed in the first 20 patients (stage 1), the treatment would be considered ineffective, and further enrollment would be discontinued.
  
  
  RESULTS
  Only 1 PR was observed in the first 20 patients. By the time of study closure, 5 additional patients who were already being screened for study inclusion were enrolled. Of the 25 patients (15 women, 10 men; 4 stage IIIB, 21 stage IV; median age, 67 years [range, 45-85 years]), there were 3 (12%) PRs and 6 (24%) cases with stable disease observed. The median time-to-progression and progression-free survival was 2.8 months. Seven (28%) patients remained progression-free at 24 weeks. No grade 3 or higher hematologic adverse events were observed. Thirteen (52%) patients had a grade 3 nonhematologic adverse event, with fatigue (20%), diarrhea (8%), and dyspnea (8%) being the most common.
  
  
  CONCLUSIONS
  Sorafenib is not effective as front-line therapy in the general unselected NSCLC population. The window of opportunity design is feasible for estimating the activity of novel compounds.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Dy
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Hillman
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.forename: Preston D
authors.initials: PD
authors.lastname: Steen
authors.forename: Donald B
authors.initials: DB
authors.lastname: Wender
authors.forename: Suresh
authors.initials: S
authors.lastname: Nair
authors.forename: Sumithra
authors.initials: S
authors.lastname: Mandrekar
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: Alex A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib