Combretastatin A-1 phosphate potentiates the antitumour activity of cisplatin in a murine adenocarcinoma model
Shnyder, S.D.; Cooper, P.A.; Pettit, G.R.; Lippert, J.W.; Bibby, M.C.
Anticancer Research 23(2b): 1619-1623
2003
ISSN/ISBN: 0250-7005 PMID: 12820431 Document Number: 553669
Background: The tubulin depolymerising 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 100mgkg-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.