Clinical pharmacokinetic advantages of new drug delivery methods for the treatment of liver tumours.

Response rates following systemic chemotherapy for hepatic tumours are disappointing. The drugs used have a narrow therapeutic ratio, which limit the scope for dose escalation of these potentially toxic agents. Therefore, alternative delivery methods that optimise the efficacy of currently available cytotoxic agents have been explored. Several novel approaches have attempted to 'target' treatment so that it reaches the tumour whilst minimising systemic exposure. There is some evidence to suggest that certain agents, including monoclonal antibodies and liposomes, selectively lodge in tumours following intravenous administration. Alternatively, the route of administration may be modified to enhance targeting of the administered drug. Delivery via the hepatic arterial, portal venous, and peritoneal routes as well as drug delivery via direct implantation may provide certain pharmacokinetic advantages. Infusion rates may be adjusted to optimise the pharmacokinetic profile. Chemoembolisation with microspheres, microcapsules or macromolecules might enhance targeting further. Variations in particle characteristics or by modifying hepatic arterial blood flow with vasoactive substances may be used to further refine this technique. The ultimate 'magic bullet', which allows total delivery of treatment to malignant cells whilst eliminating exposure of healthy tissues to these toxic agents, has not been developed as yet. However, currently available techniques allow considerable dose escalation that, whilst not providing a significant survival advantage, certainly improves response rates.