Dual targeting of tumor vasculature: combining Avastin and vascular disrupting agents (CA4P or OXi4503)

Anticancer Res. 2008 Jul-Aug;28(4B):2027-31.


Background: This study evaluated the therapeutic efficacy of combining vascular disrupting agents with antiangiogenic agents.

Materials and methods: Human clear cell renal carcinoma (Caki-1) tumors were established in nude mice. Treatments consisted of Avastin (2 mg/kg) administered twice a week; CA4P (100 mg/kg) or OXi4503 (25 mg/kg) administered 3 times a week for a period of 2 weeks; or a combination of Avastin and CA4P or OXi4503. Tumor response was assessed by growth delay.

Results: The tumor growth delays were 8, 6, and 18 days for Avastin, CA4P, and OXi4503, respectively. When the two therapies were combined, there was a significantly greater tumor response than what was achieved with single-agent treatments. For example, Avastin plus CA4P led to a growth delay of 13 days, and 27 days for Avastin plus OXi4503.

Conclusion: Vascular-directed therapies that include both antiangiogenic and vascular disrupting therapeutics can result in significantly enhanced antitumor effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Bevacizumab
  • Carcinoma, Renal Cell / blood supply*
  • Carcinoma, Renal Cell / drug therapy
  • Diphosphates / administration & dosage
  • Diphosphates / pharmacology
  • Humans
  • Kidney Neoplasms / blood supply*
  • Kidney Neoplasms / drug therapy
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Diphosphates
  • Oxi 4503
  • Stilbenes
  • Bevacizumab
  • fosbretabulin