title: Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma.
abstract: BACKGROUND
  Paragangliomas are tumors that develop from extraadrenal chromaffin cells. Approximately 20% of paragangliomas are malignant, and surgical resection is considered the primary treatment when possible. The optimal systemic treatment for advanced disease is undefined, due in part to lack of effective agents. Here we report our experience suggesting that sunitinib is an effective agent in this malignancy.
  
  
  METHODS
  Three patients with metastatic paraganglioma were treated with sunitinib at the Princess Margaret Hospital. Limited analyses of tumor tissue and germline DNA were available.
  
  
  METHODS
  Sunitinib at a standard dose (50 mg daily, 4 wk on, 2 wk off) was titrated to patient tolerance.
  
  
  RESULTS
  One patient has achieved a near complete response, and two patients demonstrated partial responses. Two patients demonstrated germline defects suggesting a pseudo-hypoxic drive to the tumor whereas the third demonstrated immunohistochemical evidence of this phenomenon.
  
  
  CONCLUSIONS
  Sunitinib appears to be an active agent in this malignancy based on this limited cohort, with an understandable mechanism of action similar to that described in other hypoxia-driven tumors. A single arm phase 2 trial is underway.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, M5G 2M9 Toronto, Ontario, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.forename: Andrew
authors.initials: A
authors.lastname: Evans
authors.forename: Reuben
authors.initials: R
authors.lastname: Broom
authors.forename: Marc
authors.initials: M
authors.lastname: Freeman
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010673:Pheochromocytoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib