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Clinical Pharmacokinetics 1994-Apr

Chemo-occlusion for the treatment of liver cancer. A new technique using degradable starch microspheres.

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The use of particulate embolic agents combined with regional chemotherapy in the treatment of hepatocellular carcinoma and metastatic liver cancer has been widely investigated over the past decade. The rationale for the use of such agents is to provide vascular blockade, resulting in a reduced or halted blood flow. This increases the in situ time, tumour exposure and, thus, efficacy of any coadministered cytotoxic drug. Of all the embolic agents and techniques available, degradable starch microspheres (DSMs) are the agents that have been evaluated most extensively. DSMs are non-toxic, are readily degradable and provide temporary vascular occlusion. Phase II and III clinical trials have demonstrated the efficacy of DSM when coadministered with chemotherapeutic drugs (chemo-occlusion), as measured by tumour response. Indeed, compared with drug therapy alone, a significantly greater tumour response is associated with chemo-occlusion, for patients with either hepatocellular carcinoma or metastatic liver cancer. The use of combination or multi-modular therapies have, in recent years, been investigated. The therapeutic benefits associated with chemo-occlusion would suggest that this technique might have a potential application as an adjuvant, or neoadjuvant therapy, for example, in reducing tumour recurrence after surgical resection in hepatocellular carcinoma, or downstaging a tumour prior to surgical resection, respectively. Furthermore, comprehensive management of patients with liver metastases and potential extrahepatic involvement may well be achieved by a combination of DSM chemo-occlusion and systemic chemotherapy. Large, randomised trials are, however, required to access more fully the clinical benefits associated with chemo-occlusion, such as, quality of life, time to tumour progression and survival. Regionally occlusive techniques administered with cytotoxic agents have also shown potential in the treatment of alternative cancers, for example, breast and pancreatic carcinomas. However, these therapies require further evaluation.

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