Corpus ID: 41363257

Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma.

  title={Combination chemotherapy with combretastatin A-4 phosphate and 5-fluorouracil in an experimental murine colon adenocarcinoma.},
  author={Konstantina Grosios and Paul M. Loadman and David J. Swaine and George R. Pettit and Michael C. Bibby},
  journal={Anticancer research},
  volume={20 1A},
The di-sodium phosphate pro-drug of combretastatin-A4(combA-4P) is undergoing Phase 1 clinical trial in the USA and UK. Its mechanism of action is thought to be related to tubulin-binding properties that result in rapid, tumour endothelial cell damage, neovascular shutdown and subsequent haemorrhagic necrosis. Drugs that work by this mechanism are unlikely to eradicate the tumour as a single agent but should potentiate standard chemotherapy. This study demonstrates that extensive necrosis… Expand
Schedule dependence of combretastatin A4 phosphate in transplanted and spontaneous tumour models
Investigation of the effects of multiple daily or twice daily dosing with CA4P on the vascular function, cell survival and growth of syngeneic and spontaneous breast cancers in mice indicates that the potential anti‐tumour activity ofCA4P when used as a single agent in clinical trials may be enhanced when used in multiple dose schedules. Expand
Marked potentiation of the antitumour activity of chemotherapeutic drugs by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)
There was a dramatic therapeutic interaction between DMXAA and standard chemotherapy drugs, particularly paclitaxel, against the MDAH-MCa-4 tumour, which was not due to a pharmacokinetic interaction or potentiation of antivascular activity. Expand
The development of combretastatin A4 phosphate as a vascular targeting agent.
  • D. Chaplin, S. Hill
  • Medicine
  • International journal of radiation oncology, biology, physics
  • 2002
Results confirm the ability of CA4P to selectively compromise vascular function in experimental tumors, inducing extensive tumor cell death at well-tolerated doses, and offer considerable potential for enhancing the effectiveness of existing and emerging cancer therapies. Expand
Phase I Trial of Combretastatin A-4 Phosphate with Carboplatin
This study of CA4P and carboplatin given in combination showed dose-limiting thrombocytopenia, and pharmacokinetic/pharmacodynamic modeling permitted the inference that alteredcarboplatin pharmacokinetics caused the increment in platelet toxicity. Expand
Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate.
It is shown that antibody-targeted radioimmunotherapy (RIT) effectively treated the well-perfused tumor rim, producing regressions for approximately 35 days, but was less effective at the more hypoxic center, and the need to consider cancer treatment in a biologically heterogeneous setting, if results are to be effectively translated to the clinic. Expand
Combretastatin A4 phosphate: background and current clinical status
Combretastatin A4 phosphate is a water-soluble prodrug of the cis-stilbene CA4 originally isolated from the tree Combretum caffrum that induces blood flow reductions and subsequent tumour cell death in a variety of preclinical models. Expand
Combination therapy studies with the vascular disruptive agentcombretastatin-a4-phosphate (CA4P)
The hypothesis that two agents may be additive or synergistic, eliminating separate tumour cell subpopulations and thus increasing the effectiveness of both drugs is examined, finding no strong relationships between DCE-MRI variable change following CA4P and the angiogenic markers. Expand
Combretastatin A4 phosphate.
Results from the first clinical trials have shown that CA4P monotherapy is safe and reduces tumor blood flow, and CA5P in combination with cisplatin is also safe and safe. Expand
Combretastatin A-4-phosphate effectively increases tumor retention of the therapeutic antibody, 131I-A5B7, even at doses that are sub-optimal for vascular shut-down.
It is demonstrated that moderate tumor blood flow reduction following antibody administration is sufficient to improve tumor antibody retention and is encouraging for the combination of CA-4-P and 131I-A5B7 in clinical trials. Expand
Combretastatin A-4 phosphate enhances CPT-11 activity independently of the administration sequence.
CA4DP significantly enhances the antitumour effect of CPT-11, which is not greatly influenced by the administration sequence, and which lacks a correlation with the intratumoral trapping of C PT-11 or SN-38. Expand