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


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.


CONCLUSIONS
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.
Shnyder
S D
SD
Cancer Research Unit, Tom Connors Cancer Research Centre, University of Bradford, Richmond Road, Bradford BD7 1DP, U.K. S.D.Shnyder@Bradford.ac.uk
Cooper
P A
PA
Pettit
G R
GR
Lippert
J W
JW
Bibby
M C
MC
D002288:Adenocarcinoma, Mucinous / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D013267:Stilbenes; C063690:combretastatin A-1; D002945:Cisplatin