title: Brief report: a phase II study of sunitinib in malignant pleural mesothelioma. the NCIC Clinical Trials Group.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is an aggressive malignancy that most often presents at an advanced, incurable stage. After the failure of standard first-line cisplatin/antifolate chemotherapy, there is no accepted treatment. The vascular endothelial growth factor pathway may be a relevant therapeutic target in MPM.
  
  
  METHODS
  This open-labeled phase II trial evaluated single-agent sunitinib, an inhibitor of multiple receptor tyrosine kinases including the vascular endothelial growth factor receptors, given at 50 mg daily orally for 4 weeks followed by a 2-week rest, in patients with advanced MPM. Two cohorts were studied: cohort 1, in which patients had previously received cisplatin-based chemotherapy, and cohort 2, consisting of previously untreated patients. A two-stage design was used for both cohorts; the primary outcome was objective response rate as determined by the RECIST criteria modified for MPM. Secondary outcomes included rates and duration of disease control, progression-free survival and overall survival, and safety and tolerability.
  
  
  RESULTS
  A total of 35 eligible patients were enrolled (17 to cohort 1 and 18 to cohort 2). Neither cohort met the criteria for continuing to the second stage of accrual; only one objective response, confirmed by independent review, was observed in a previously untreated patient. Median progression-free and overall survivals were 2.8 and 8.3 months in cohort 1, and 2.7 and 6.7 months in cohort 2, respectively. Observed toxicity was within that expected for sunitinib.
  
  
  CONCLUSIONS
  Sunitinib, similar to other angiogenesis inhibitors, has limited activity in MPM. Future trials of angiogenesis inhibitors given as single agents in unselected patients with MPM are not warranted.
authors: The NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, Canada. slaurie@toh.on.ca
authors: Scott A
authors: SA
authors: Laurie
authors: Ashish
authors: A
authors: Gupta
authors: Quincy
authors: Q
authors: Chu
authors: Christopher W
authors: CW
authors: Lee
authors: Wojciech
authors: W
authors: Morzycki
authors: Ronald
authors: R
authors: Feld
authors: Alison H
authors: AH
authors: Foo
authors: Jean
authors: J
authors: Seely
authors: John R
authors: JR
authors: Goffin
authors: Francis
authors: F
authors: Laberge
authors: Nevin
authors: N
authors: Murray
authors: Sanjay
authors: S
authors: Rao
authors: Garth
authors: G
authors: Nicholas
authors: Janessa
authors: J
authors: Laskin
authors: Tony
authors: T
authors: Reiman
authors: Delia
authors: D
authors: Sauciuc
authors: Lesley
authors: L
authors: Seymour
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; 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; D011758:Pyrroles / Q000627:therapeutic use*; D016879:Salvage Therapy; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib