Pharmacokinetics of intra-arterial chemotherapy.

Advanced or aggressive, but localised, malignancies can often be reduced to more curable proportions by the use of "basal chemotherapy", that is, using chemotherapy as the first mode of treatment, prior to definitive radiotherapy and/or surgical excision. In using anticancer agents, drug combinations, timing and methods of administration are employed which exploit differences between cancer cells and normal tissues and cells. One exploitable difference which is often overlooked is the fact that localised tumour is often supplied with blood by one artery; this can be cannulated so that the agents used can be delivered selectively in high concentration to the region containing the tumour. The advantage in delivering drugs regionally by intra-arterial infusion depends upon the size of the artery infused, the rate of excretion or detoxification of the agents used, the amount of the agent infused entering the tissues - especially from the first circulation, and especially the amount of agent entering the tissues which is biologically active against tumour cells. Taking all these factors into account, mathematical calculations indicated that under the worst possible circumstances infusion of anticancer agents intra-arterially should be at least 1.8 times more effective regionally than intravenous administration. In most situations and with most agents used the advantage would be significantly greater than this. These calculations are supported by evidence in the literature and by observations of a greater regional effect, albeit toxic, of intra-arterial administration of the agents. These effects include more pronounced loss of hair in the region of distribution of the artery infused, and increased skin and mucosal ulceration in the distribution of the artery infused. The disadvantage of using intra-arterial infusion delivery is the need for hospitalisation. Therefore, properly controlled, randomised clinical trials should be conducted to compare clinical results of intra-arterial and intravenous chemotherapy administration.