title: A phase II study of sunitinib in recurrent and/or metastatic adenoid cystic carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) and c-kit are highly expressed in adenoid cystic carcinoma (ACC) and associated with biologic aggressiveness. This study aimed to assess the antitumor activity of sunitinib, a multi-targeted inhibitor of vascular endothelial growth factor receptor, c-kit, platelet-derived growth factor receptor, ret proto-oncogene (RET) and FMS-like tyrosine kinase 3 (FLT3), in ACC of the salivary gland.
  
  
  METHODS
  Patients with progressive, recurrent and/or metastatic ACC were treated with sunitinib 37.5 mg daily in this single-arm, two-stage phase II trial. Response was assessed every 8 weeks.
  
  
  RESULTS
  Fourteen patients were enrolled on to the study. Among 13 assessable patients, there were no objective responses, 11 patients had stable disease (SD), 8 patients had SD ≥ 6 months and 2 patients had progressive disease as best response. Median time to progression was 7.2 months. Median overall survival was 18.7 months. Toxic effects occurring in at least 50% of patients included fatigue, oral mucositis and hypophosphatemia usually of mild to moderate severity.
  
  
  CONCLUSIONS
  Although no responses were observed, sunitinib was well tolerated, with prolonged tumor stabilization of ≥ 6 months in 62% of assessable patients. The lack of responses is comparable with other trials of molecularly targeted agents in ACC and highlights the need for novel strategies in phase II clinical trial design.
authors.affiliation: Princess Margaret Hospital, University Health Network, Toronto, Canada.
authors.forename: N G
authors.initials: NG
authors.lastname: Chau
authors.forename: S J
authors.initials: SJ
authors.lastname: Hotte
authors.forename: E X
authors.initials: EX
authors.lastname: Chen
authors.forename: S F
authors.initials: SF
authors.lastname: Chin
authors.forename: S
authors.initials: S
authors.lastname: Turner
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: L L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local; D000090063:Proto-Oncogene Mas; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011758:Pyrroles; D000077210:Sunitinib