Combretastatin A-1 phosphate potentiates the antitumour activity of cisplatin in a murine adenocarcinoma model

Anticancer Res. 2003 Mar-Apr;23(2B):1619-23.

Abstract

Background: The tubulin depolymerizing drug Combretastatin A-1 phosphate (CA1P), a water-soluble derivative of combretastatin A-1, has been recently shown to have a better efficacy in experimental models than the clinically active, close structural analogue, combretastatin A-4 phosphate (CA4P). Previous studies with CA4P in combination with standard anti-cancer agents have demonstrated improved efficacy relative to the standard agents.

Materials and methods: In this study the synergistic effects of administering CA1P in combination with cisplatin (CPL) in a well-differentiated transplantable murine colon model (MAC 29) was evaluated.

Results: CA1P at 100 mgkg-1 significantly potentiated the anti-tumour effects of CPL. The effect with CPL was similar to that seen for CA1P at its maximum tolerated dose (MTD) alone.

Conclusion: These data demonstrate that the combination of CA1P and CPL has significant preclinical antitumour activity against a transplantable murine adenocarcinoma model that is related to the antivascular effects of CA1P.

Publication types

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

MeSH terms

  • Adenocarcinoma, Mucinous / blood supply
  • Adenocarcinoma, Mucinous / drug therapy*
  • Adenocarcinoma, Mucinous / pathology
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology*
  • Cisplatin / therapeutic use
  • Colonic Neoplasms / pathology*
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Stilbenes / administration & dosage
  • Stilbenes / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Stilbenes
  • combretastatin A-1
  • Cisplatin