title: Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer.
abstract: OBJECTIVE
  Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor kinase activity. The activity of vandetanib plus docetaxel was assessed in patients with previously treated non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This two-part study comprised an open-label run-in phase and a double-blind randomized phase. Eligible patients had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of first-line platinum-based chemotherapy. The primary objective of the randomized phase was to prolong progression-free survival (PFS) in patients receiving vandetanib (100 or 300 mg/d) plus docetaxel (75 mg/m2 intravenous infusion every 21 days) versus placebo plus docetaxel. The study was designed to have more than 75% power to detect 50% prolongation at a one-sided significance level of P < .20. Secondary objectives included objective response rate, overall survival, safety and tolerability.
  
  
  RESULTS
  In the randomized phase (n = 127), median PFS was 18.7 weeks for vandetanib 100 mg plus docetaxel (n = 42; hazard ratio v docetaxel = 0.64; one-sided P = .037); 17.0 weeks for vandetanib 300 mg plus docetaxel (n = 44; hazard ratio v docetaxel = 0.83; one-sided P = .231); and 12 weeks for docetaxel (n = 41). There was no statistically significant difference in overall survival among the three treatment arms. Common adverse events included diarrhea, rash, and asymptomatic prolongation of corrected QT (QTC) interval.
  
  
  CONCLUSIONS
  The primary objective was achieved, with vandetanib 100 mg plus docetaxel demonstrating a significant prolongation of PFS compared with docetaxel in relation to the prespecified significance level. On the basis of these encouraging data, phase III evaluation of vandetanib 100 mg plus docetaxel in second-line NSCLC has been initiated.
authors: Dana-Farber Cancer Institute, Boston, MA, USA.
authors: John V
authors: JV
authors: Heymach
authors: Bruce E
authors: BE
authors: Johnson
authors: Diane
authors: D
authors: Prager
authors: Edit
authors: E
authors: Csada
authors: Jaromír
authors: J
authors: Roubec
authors: Milos
authors: M
authors: Pesek
authors: Irena
authors: I
authors: Spásová
authors: Chandra P
authors: CP
authors: Belani
authors: István
authors: I
authors: Bodrogi
authors: Shirish
authors: S
authors: Gadgeel
authors: Sarah J
authors: SJ
authors: Kennedy
authors: Jeannie
authors: J
authors: Hou
authors: Roy S
authors: RS
authors: Herbst
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D010919:Placebos; D011799:Quinazolines / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D010880:Piperidines; D010919:Placebos; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; C452423:vandetanib