Intra-hepatic arterial drug delivery

In this review, the pharmacokinetic rationale for hepatic arterial drug therapy is discussed, along with techniques that have been developed in order to try to enhance the regional advantage accrued from this route of administration. Clinical trials of hepatic arterial therapy in patients with primary hepatocellular carcinoma and with liver metastases from colorectal carcinoma are discussed. Although clinical response rates am significantly better with regional as compared with systemic therapy, survival is not prolonged. This is mainly due to the development of extrahepatic metastases. A treatment strategy using high dose hepatic arterial 5-fluorouracil (5-FU) infusion with the deliberate aim of achieving maximum tolerated systemic drug levels has entered phase III clinical trial. Monitoring of in vivo tumour pharmacokinetics using F-19 magnetic resonance spectroscopy and F-18-5-FU positron emission tomography (PET) demonstrate elegantly how target drug uptake may be assessed. We plan to use PET to monitor intra-tumoral viral transduction and 5-flucytosine conversion rates to active 5-FU in our hepatic arterial pro-drug gene therapy programme soon to enter clinical trial.