CLINICAL PHARMACOKINETIC ADVANTAGES OF NEW DRUG-DELIVERY METHODS FOR THE TREATMENT OF LIVER-TUMORS

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 nove l approaches have attempted to 'target' treatment so that it reaches t he tumour whilst minimising systemic exposure. There is some evidence to sug gest that certain agents, including monoclonal antibodies and l iposomes, selectively lodge in tumours following intravenous administr ation. Alternatively, the route of administration may be modified to e nhance targeting of the administered drug. Delivery via the hepatic ar terial, 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 profi le. Chemoembolisation with microspheres, microcapsules or macromolecul es might enhance targeting further. Variations in particle characteris tics or by modifying hepatic arterial blood flow with vasoactive subst ances may be used to further refine this technique. The ultimate 'magi c 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 technique s allow considerable dose escalation that, whilst not providing a sign ificant survival advantage, certainly improves response rates.