title: Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma.
abstract: OBJECTIVE
  This multicenter, open-label, phase II study evaluated the safety and clinical activity of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2, and 3, in patients with metastatic melanoma.
  
  
  METHODS
  Thirty-two patients with a maximum of one prior systemic therapy received axitinib at a starting dose of 5 mg twice daily. The primary endpoint was objective response rate.
  
  
  RESULTS
  Objective response rate was 18.8% [95% confidence interval (CI), 7.2-36.4], comprising one complete and five partial responses with a median response duration of 5.9 months (95% CI, 5.0-17.0). Stable disease at 16 weeks was noted in six patients (18.8%), with an overall clinical benefit rate of 37.5%. Six-month progression-free survival rate was 33.9%, 1-year overall survival rate was 28.1%, and median overall survival was 6.6 months (95% CI, 5.2-9.0). The most frequently (>15%) reported nonhematologic, treatment-related adverse events were fatigue, hypertension, hoarseness, and diarrhea. Treatment-related fatal bowel perforation, a known class effect, occurred in one patient. Axitinib selectively decreased plasma concentrations of soluble VEGFR (sVEGFR)-2 and sVEGFR-3 compared with soluble stem cell factor receptor (sKIT). No significant association was noted between plasma levels of axitinib and response. However, post hoc analyses indicated potential relationships between efficacy endpoints and diastolic blood pressure of 90 mm Hg or higher as well as baseline serum lactate dehydrogenase levels.
  
  
  CONCLUSIONS
  Axitinib was well tolerated, showed a selective VEGFR-inhibitory profile, and showed single-agent activity in metastatic melanoma. Further evaluations of axitinib, alone and combined with chemotherapy, are ongoing.
authors: University of California, Irvine, Orange, 92868, USA. johnfruehauf@msn.com
authors: John
authors: J
authors: Fruehauf
authors: Jose
authors: J
authors: Lutzky
authors: David
authors: D
authors: McDermott
authors: Charles K
authors: CK
authors: Brown
authors: Jean-Baptiste
authors: JB
authors: Meric
authors: Brad
authors: B
authors: Rosbrook
authors: David R
authors: DR
authors: Shalinsky
authors: Katherine F
authors: KF
authors: Liau
authors: Andreas G
authors: AG
authors: Niethammer
authors: Sinil
authors: S
authors: Kim
authors: Olivier
authors: O
authors: Rixe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077784:Axitinib; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; D019009:Proto-Oncogene Proteins c-kit; D040262:Receptors, Vascular Endothelial Growth Factor