Vinflunine potentiates the activity of cisplatin but not 5-fluorouracil in a transplantable murine adenocarcinoma model.
BACKGROUND
Vinflunine is a novel Vinca alkaloid currently undergoing Phase II clinical trials, which have previously demonstrated anti-vascular effects in a transplantable murine colon adenocarcinoma model. Previous studies with compounds showing similar effects in combination with standard anti-cancer agents have demonstrated an improved efficacy relative to the standard agents.


METHODS
In this study the synergistic effects of administering vinflunine in combination with either Cisplatin (CPL) or 5-fluorouracil (5-FU) were investigated in a well-differentiated transplantable murine colon adenocarcinoma model (MAC 29).


RESULTS
Vinflunine significantly potentiated the anti-tumour effects of CPL, but had little effect in combination with 5-FU. Using Hoescht 33342 dye labelling of the functional vasculature, clear evidence of vascular shutdown was seen for treatment groups including vinflunine.


CONCLUSIONS
These data demonstrate that the combination of vinflunine and CPL has significant preclinical anti-tumour activity against a transplantable murine adenocarcinoma model that is related to the anti-vascular effects of vinflunine.
Cancer Research Unit, Tom Connors Cancer Research Centre, University of Bradford, Richmond Road, Bradford BD7 1DP, U.K. S.D.Shnyder@Bradford.ac.uk
S D
SD
Shnyder
P A
PA
Cooper
N
N
Gyselinck
B T
BT
Hill
J A
JA
Double
M C
MC
Bibby
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*
C111217:vinflunine; D014747:Vinblastine; D002945:Cisplatin; D005472:Fluorouracil