Anti—vascular approaches to solid tumour therapy: Evaluation of vinblastine and flavone acetic acid
✍ Scribed by Sally A. Hill; Louise E. Sampson; David J. Chaplin
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 552 KB
- Volume
- 63
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Several agents have now been identified which exert their anti‐tumour effects in large part via the tumour vasculature; these include TNFα and flavone acetic acid (FAA). More recently, Vincristine and Vinblastine have also been shown to cause a prolonged and selective decrease in tumour perfusion. Vinblastine, unlike FAA, causes no increase in plasma TNFα levels in mice bearing the CaNT tumour, suggesting 2 distinct mechanisms of anti‐vascular activity for these structurally diverse agents. Since FAA and Vinblastine also show quite different normal tissue toxicities, which are separately dose‐limiting, we have examined the strategy of combining these 2 agents. When Vinblastine preceded FAA by 24 hr or less, tumour growth delay was significantly enhanced without a concomitant increase in toxicity. The level of enhancement was not significantly reduced by a 5‐fold decrease in Vinblastine dose, though any reduction in the dose of FAA caused a rapid reduction in treatment effectiveness. Investigation of the functional vasculature of treated tumours suggested that increased anti‐vascular effects may contribute to the enhanced growth inhibition of the combined treatment. Our results demonstrate the potential benefit of combining 2 different classes of antivas‐cular agent, using Vinblastine and FAA (or 5,6‐MeXAA) as prototype drugs.