title: Vandetanib plus chemotherapy for induction followed by vandetanib or placebo as maintenance for patients with advanced non-small-cell lung cancer: a randomized phase 2 PrECOG study (PrE0501).
abstract: BACKGROUND
  After early reports of vandetanib's efficacy in the induction setting, we evaluated the effect of combination docetaxel, carboplatin, and vandetanib, followed by maintenance therapy with either vandetanib, or placebo on progression-free survival (PFS) in patients with advanced non-small-cell lung cancer.
  
  
  METHODS
  Patients with advanced non-small-cell lung cancer were randomized to induction docetaxel (75 mg/m) + carboplatin (area under the curve of 6) on day 1 of a 21-day cycle, and daily vandetanib (100 mg/day orally) for four cycles, followed by daily vandetanib (300 35 mg/day orally) or placebo until progression. Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 of 1, and no prior cytotoxic or targeted agents for advanced disease.
  
  
  RESULTS
  One hundred sixty-two patients were randomized; 158 began induction treatment. Fifty-eight patients began maintenance vandetanib or placebo (median, 3.5 cycles). Median PFS for patients randomized to maintenance vandetanib was 4.5 months (95% confidence interval, 3.3-5.8 months), and for patients randomized to maintenance placebo was 4.2 months (95% confidence interval, 2.8-4.9 months). An exploratory analysis showed prolonged PFS for patients randomized to vandetanib maintenance (stratified log-rank p= 0.07) as also in a multivariate model adjusting for sex and stage (p= 0.02). Differences in PFS were not observed among patients who began maintenance therapy. Toxicities were similar to other studies of these agents.
  
  
  CONCLUSIONS
  Neither arm showed improvement over historical median PFS of 4.6 months, although patients who began maintenance and were randomized to vandetanib had somewhat better outcomes than those randomized to placebo. Given its acceptable toxicity profile, there may be a role for vandetanib in maintenance.
authors.affiliation: Department of Medical Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, USA
authors.forename: Joseph
authors.initials: J
authors.lastname: Aisner
authors.forename: Judith B
authors.initials: JB
authors.lastname: Manola
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stella
authors.forename: Mika A
authors.initials: MA
authors.lastname: Sovak
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
mesh_terms: 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* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib