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

Lingyun Li, Amyn M. Rojiani, Dietmar W. Siemann

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49 Citations (Scopus)

Abstract

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 ∼ 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.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalActa Oncologica
Volume41
Issue number1
DOIs
StatePublished - Apr 20 2002
Externally publishedYes

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Kaposi's Sarcoma
Blood Vessels
Heterografts
Cisplatin
Therapeutics
Neoplasms
Growth
Drug Therapy
Vinblastine
Radiation Effects
fosbretabulin
Nude Mice
Cell Survival
Acquired Immunodeficiency Syndrome
Radiation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

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abstract = "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 ∼ 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.",
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