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.
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.
Li
Lingyun
L
Department of Pharmacology and Experimental Therapeutics , Shands Cancer Center, University of Florida, Gainesville 32610, USA.
Rojiani
Amyn M
AM
Siemann
Dietmar W
DW
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008819:Mice, Nude; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D012514:Sarcoma, Kaposi / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors; D014410:Tumor Stem Cell Assay; D014747:Vinblastine / Q000008:administration & dosage; D014916:Whole-Body Irradiation
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D014747:Vinblastine; C058728:fosbretabulin; D002945:Cisplatin