External carotid artery infusion with single-and multiple-drug regimens in the rat.

An animal model was constructed using retrograde cannulation of a branch of the external carotid artery of rats in order to study the intraarterial (IA) and systemic effects of bleomycine, methotrexate, and 5-fluorouracil on a squamous cell carcinoma implanted in both ears. Continuous seven-day IA infusion of bleomycine and 5-fluorouracil proved to be superior to the systemic way by about a factor of 3. Unfortunately, the tumor did not respond to methotrexate and therefore, for this drug, no conclusion could be made as to the relative benefits of IA administration. Comparing simultaneous, sequential, and intermittent multiple-drug regimens, the last one showed an antitumor effect which was superior to either of the other schedules. It is concluded that IA administration of effective cytotoxic drugs is a superior treatment modality and that in this model IA intermittent multiple-drug therapy is the most successful schedule yet studied.