A randomized Phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer

Clin Cancer Res. 2004 May 15;10(10):3365-70. doi: 10.1158/1078-0432.CCR-03-0404.


Purpose: To assess the activity of the antiangiogenic agent and VEGFR2 inhibitor SU5416 in hormone-refractory prostate cancer.

Patients and methods: Thirty-six chemotherapy naïve patients were randomized to treatment with SU5416 (145 mg/m(2)) and dexamethasone premedication or dexamethasone alone. Patients in the control arm could cross over to experimental therapy after progression. Prostate-specific antigen (PSA) was measured every 2 weeks, and radiological evaluation was performed every 8 weeks. In vitro assessment of SU5416 on PSA secretion was assessed in the LNCaP cell line. Baseline serum basic fibroblast growth factor and plasma vascular endothelial growth factor (VEGF) were explored as prognostic factors.

Results: VEGF receptor-2 expression is detectable in prostate cancer cell lines, and SU5416 inhibited in vitro PSA secretion. No effect of SU5416 on PSA secretion or time to progression is detectable in patients. VEGF and basic fibroblast growth factor were not prognostic. Headache and fatigue were the most common SU5416 toxicities, but hyperglycemia, hyponatremia, lymphopenia, infection, and adrenal suppression, all attributable to steroids and the required central line, were common.

Conclusion: No disease modifying effects of SU5416 were detectable in this small study. Modest toxicity, an inconvenient administration schedule, and availability of other VEGFR-targeted agents support the decision to halt further evaluation of SU5416 in prostate cancer.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Dexamethasone / therapeutic use
  • Dose-Response Relationship, Drug
  • Fibroblast Growth Factors / blood
  • Humans
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Pyrroles / therapeutic use*
  • Time Factors
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors


  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • Indoles
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors
  • Semaxinib
  • Dexamethasone
  • Vascular Endothelial Growth Factor Receptor-2
  • Prostate-Specific Antigen