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Excerpt
Systemic chemotherapy has been tried for inoperable hepatocellular carcinoma using adriamycin, fluorouracil, mitomycin, and cisplatin alone or in combinations. Response rates generally do not exceed 20%, and overall success of systemic chemotherapy is poor because the narrow therapeutic ratio precludes dose escalation. This has led to alternative routes of drug delivery; direct drug injection into the tumor, intraperitoneal application, and intraportal or intra-arterial infusion all have been tried to achieve higher intratumoral drug concentrations compared with systemic levels. The latter concept of intra-arterial application of cytotoxic agents is particularly attractive because primary and secondary liver tumors are vascularized predominantly by the arterial route. At least this is true for small lesions, which seem to be almost exclusively dependent on arterial supply, whereas larger lesions attract some degree of portal venous blood supply in the periphery of the tumor bordering on normal hepatic tissue. This dual vascular supply of the liver and the predominant arterial supply of tumor tissue has been used for the selective application of drugs to achieve higher intratumoral levels of chemotherapeutic agents compared with normal liver tissue and systemic drug levels. This specific vascular anatomy also has been taken advantage of when permanent ligation or intermittent occlusion of the hepatic artery was used to treat hepatic tumors.
The combination of selective hepatic vascular occlusion and similarly selective intra-arterial or intraportal administration of cytotoxic drugs has been termed chemoembolization. Vascular occlusion can been achieved at different vascular levels (such as larger arterioles or venules as opposed to capillary vascular occlusion) by using appropriate materials. Currently, the most commonly employed materials for hepatic artery or portal embolization are lipiodol, starch microspheres, lyophilized dura, and gel foam particles. The selectivity of routing the occlusive material to the intratumoral vascular bed can be increased by preocclusion application of norepinephrine, epinephrine, or glycylpressine. These drugs cause a reduction of blood flow to normal liver tissue, but cause vasoconstriction of tumor vessels only to a lesser degree. Selective embolization of tumor vessels subsequently has been combined with the administration of cytotoxic drugs or using iodine 131-labelled antiferritin or lipoidal to achieve a higher concentration of these compounds in the tumor tissue for a prolonged time period. The most commonly used drugs are anthracyclines, mitomycin, cisplatin, and fluorouracil Using this approach, a higher response rate can be observed, but three randomized and controlled trials of palliative chemoembolization have failed to record significant improvement of survival in patients with inoperable disease.1-3 One trial determined a temporary benefit from embolization when compared with fluorouracil alone.4 Another small trial found that embolization with iodine 131-lipoidal significantly increased survival compared with untreated controls.
