Increasing the Uptake of a Low Molecular Weight Marker in Liver Tumours by Degradable Starch Microspheres: Possible Mechanisms of Action

Abstract

The prognosis for patients with hepatic metastases remains poor despite the increasing number of treatments available to the physician. The results of recent trials show that there has been no benefit in terms of survival with systemic chemotherapy [12], irradiation [3] or hepatic dearterialisation [2]. However, there is a sound rationale for treating hepatic tumours by manipulating their arterial blood supply [8]. As the tumour grows, its nutritional and blood supply is derived almost wholly from the hepatic artery, whereas normal liver tissue has a dual blood supply dominated by the portal vein. The preliminary results from several prospective randomised trials of regional chemotherapy look to be promising [5, 6] but it is becoming clear that merely infusing the cytotoxic drug into the hepatic artery is inadequate and that further manipulation of the tumour’s blood supply could potentially improve drug delivery to tumor [1]. A variety of methods have been employed to alter tumour blood flow, one such technique being temporary arterial embolisation with degradable starch microspheres (DSM; Spherex, Pharmacia, Sweden). These microspheres, with a mean diameter of 45 μm, consist of starch polymers cross-linked with epichlorhydrine. They are degraded in vivo by endogenous serum α-amylase and have a half-life in human serum of about 20–30 min. Therefore treatment with these microspheres is readily repeatable. Regionally delivered drugs given concomitantly with DSM are retained for longer in the liver than when the drug is given alone [10].