The Treatment of Malignant Disease by Regional Chemotherapy

THE treatment of cancer by the local application of chemical substances has been practised since the time of Hippocrates. Moore, writing in the British Medical Journal of 1866, commented on the failure of occasional applications of caustic pastes in the treatment of cancer and suggested the necessity for a long continued stream of the medicinal agent flowing through the tumour. Modern chemotherapy of solid tumours began about 1940 when nitrogen mustard was first used in the treatment of the reticuloses. Klopp and his colleagues (1950) first described a method of localised chemotherapy for tumours in an area with an accessible arterial blood supply. Intermittent injections of nitrogen mustard given through a small polythene catheter in the appropriate artery produced regressions of tumour growth which had not been obtained by systemic chemotherapy. The amount of chemotherapeutic agent given by intra-arterial injection was limited, because of the general toxic effects produced after the drug had passed through the tumour circulation. The ideal agent for this form of treatment would be a substance with a very short effective life in the body after injection so that the drug was completely inactivated by the time it had passed through the tumour circulation. This type of substance has not been produced but research continues along these lines. Two methods have been developed which aim at increasing the local or regional cytotoxic effects and at the same time reducing the general toxic actions of the drugs. The first consists of vascular isolation of the region to be treated with maintenance of the circulation of the isolated area by a pump oxygenator during treatment. The second consists of injecting large doses of the drug intra-arterially and at the same time giving an antagonist to the cytotoxic agent by systemic injection. The highest concentration of the drug occurs in the treated area and severe toxicity is avoided. The majority of chemotherapeutic agents which have been used fall into two niain groups, the alkylating agents and the antimetabolites. All these substances produce their biological effects by interfering with nucleic acid synthesis. The alkylating agents act by direct chemical reaction with the complex nucleic acid molecules and so destroy their normal function. Antimetabolites, on the other hand, interfere with the synthesis of nucleic acids by competing with normal metabolites for enzymes required in nucleic acid production. Alkylating agents act rapidly and most of them exert their maximum effect within minutes …