title: Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG S0509.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.
  
  
  METHODS
  Patients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.
  
  
  RESULTS
  Fifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.
  
  
  CONCLUSIONS
  Cediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib.
authors.affiliation: Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA. lgarland@azcc.arizona.edu
authors.forename: Linda L
authors.initials: LL
authors.lastname: Garland
authors.forename: Kari
authors.initials: K
authors.lastname: Chansky
authors.forename: Antoinette J
authors.initials: AJ
authors.lastname: Wozniak
authors.forename: Anne S
authors.initials: AS
authors.lastname: Tsao
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.forename: Claire F
authors.initials: CF
authors.lastname: Verschraegen
authors.forename: Marco A
authors.initials: MA
authors.lastname: Dasilva
authors.forename: Mary
authors.initials: M
authors.lastname: Redman
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage*; D015996:Survival Rate; D007211:Indoles
chemical_list: D011799:Quinazolines; C500926:cediranib; D007211:Indoles