Preclinical evaluations of therapies combining the vascular targeting agent combretastatin A-4 disodium phosphate and conventional anticancer therapies in the treatment of Kaposi's sarcoma

Acta Oncol. 2002;41(1):91-7. doi: 10.1080/028418602317314127.


The antitumor efficacy of the vascular targeting agent combretastatin A-4 disodium phosphate (CA4DP) was evaluated in a xenograft model of Kaposi's sarcoma (KS) grown in athymic mice. Response to CA4DP alone or in combination with localized radiation treatment or systemic chemotherapy (cisplatin or vinblastine) was assessed using a clonogenic cell survival or tumor growth delay assay. Administering increasing doses of CA4DP to tumor-bearing mice resulted in a dose-dependent increase in tumor cell kill. CA4DP also enhanced the antitumor effects of radiation and chemotherapy approximately 10-100-fold. Although single doses of CA4DP as large as 300 mg/kg failed to alter tumor growth, the same total dose, administered as 3 fractions in 5 or 9 days, resulted in significant growth delay. Such repeated CA4DP exposures also significantly increased the response of KS xenografts to cisplatin. These findings suggest that CA4DP ought to be considered as a candidate agent for therapeutic evaluation in AIDS-KS patients.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell Division / drug effects
  • Cisplatin / administration & dosage
  • Drug Evaluation, Preclinical
  • Mice
  • Mice, Nude
  • Sarcoma, Experimental / blood supply
  • Sarcoma, Experimental / drug therapy*
  • Sarcoma, Experimental / radiotherapy
  • Sarcoma, Kaposi / blood supply
  • Sarcoma, Kaposi / drug therapy*
  • Sarcoma, Kaposi / radiotherapy
  • Stilbenes / therapeutic use*
  • Time Factors
  • Tumor Stem Cell Assay
  • Vinblastine / administration & dosage
  • Whole-Body Irradiation


  • Antineoplastic Agents, Phytogenic
  • Stilbenes
  • Vinblastine
  • fosbretabulin
  • Cisplatin