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

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.

• Authors: S D Shnyder, P A Cooper, G R Pettit, J W Lippert 3rd, M C Bibby
• Journal: Anticancer research (Anticancer Res) 2003 Mar-Apr Vol. 23 Issue 2B Pg. 1619-23 ISSN: 0250-7005 [Print] Greece
• PMID: 12820431 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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