Combretastatin A-4 phosphate enhances CPT-11 activity independently of the administration sequence.

Abstract

We evaluated the effect of different intervals and sequences of the vascular targeting agent combretastatin A-4 disodium phosphate (CA4DP) and CPT-11 administration on tumour growth delay and intratumoral uptake of CPT-11 using a syngeneic rhabdomyosarcoma tumour model. Irrespective of the administration sequence, the combination of CA4DP and CPT-11 significantly increases tumour growth delay in comparison with both drugs alone (P<0.001). Intratumoral CPT-11 concentration generally decreased (up to 5-fold) in the combination groups, while SN-38, the active metabolite of CPT-11, increased up to 9-fold. However, the increased amount of intratumoral SN-38 trapping after CA4DP injection did not correlate with the observed tumour growth delay. In conclusion, 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 CPT-11 or SN-38. Mechanisms other than trapping are likely to be involved in the chemosensitising capacity of CA4DP.

• Authors: H Wildiers, B Ahmed, G Guetens, G De Boeck, E A de Bruijn, W Landuyt, A T van Oosterom
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 40 Issue 2 Pg. 284-90 (Jan 2004) ISSN: 0959-8049 [Print] England
• PMID: 14728944 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Stilbenes
• Irinotecan
• fosbretabulin
• Camptothecin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Camptothecin (administration & dosage, analogs & derivatives, metabolism)
• Cell Division (drug effects)
• Drug Interactions
• Drug Synergism
• Humans
• Irinotecan
• Neoplasm Transplantation
• Rats
• Rhabdomyosarcoma (drug therapy, metabolism, pathology)
• Stilbenes (administration & dosage, metabolism)
• Time Factors
• Tumor Cells, Cultured