title: A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma.
abstract: OBJECTIVE
  A two stage multi-institution Phase II study was undertaken by the Princess Margaret Hospital Consortium to evaluate the efficacy and toxicity of oral cediranib, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with previously untreated advanced malignant melanoma.
  
  
  METHODS
  Between May 2006 and April 2008, 24 patients (median age 65 years) with advanced malignant melanoma were treated with oral cediranib. Cediranib was given on a continuous, oral once daily schedule of 45 mg, on a 28 day cycle.
  
  
  RESULTS
  Of the 17 patients evaluable for response, there was stable disease in 8 patients, and progressive disease in 9 patients, with no objective responses seen. Only 2 patients had stable disease >/= 6 months, thus the study was terminated at the end of stage 1 accrual. The overall median survival was 9.9 months, and the median time to progression was 3.5 months. The most frequent non-hematologic adverse events were hypertension (78%), fatigue (69%), diarrhea (69%) and anorexia and nausea (each 57%).
  
  
  CONCLUSIONS
  Although 2 patients had stable disease at 6 months, the short median time to progression and lack of any objective responses indicate that single agent cediranib at this dose and schedule is not sufficiently active to warrant study continuation.
authors: Department of Medical Oncology, Juravinski Cancer Centre, Hamilton Health Sciences Centre, Hamilton, ON, Canada. emcwhirt@hhsc.ca.
authors: Elaine
authors: E
authors: McWhirter
authors: Department of Medical Oncology, Princess Margaret Cancer Centre, Drug Development Program, Toronto, ON, Canada.
authors: Ian
authors: I
authors: Quirt
authors: University of Chicago Medical Centre, Chicago, IL, USA.
authors: Thomas
authors: T
authors: Gajewski
authors: Ontario Clinical Oncology Group, McMaster University, Hamilton, ON, Canada.
authors: Gregory
authors: G
authors: Pond
authors: Department of Medical Oncology, Princess Margaret Cancer Centre, Drug Development Program, Toronto, ON, Canada.
authors: Lisa
authors: L
authors: Wang
authors: Department of Medical Oncology, Princess Margaret Cancer Centre, Drug Development Program, Toronto, ON, Canada.
authors: June
authors: J
authors: Hui
authors: Department of Medical Oncology, Princess Margaret Cancer Centre, Drug Development Program, Toronto, ON, Canada.
authors: Amit
authors: A
authors: Oza
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles
chemical_list: D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C500926:cediranib; D007211:Indoles
keywords: Cediranib; First line therapy; Metastatic melanoma; Phase II trial; Vascular endothelial growth factor (VEGF)