An experimental perfusion system using the rabbit Vx-2 carcinoma. I. Studies on the effect of drug perfusions and irradiation

An experimental system, employing a small modification of the Kay-Cross disk oxygenator and rabbits with Vx-2 carcinoma transplanted to both hind limbs, has been used for evaluation of regional perfusion techniques. With this system a spectrum of agents was studied which included alkylating agents (HN2 and cyclophosphamide), antimetabolites (Methotrexate and FUdR) and antibiotics (actinomycin D and mitomycin C). One hour perfusion with Methotrexate or FUdR was without effect on this tumor system. The effect of actinomycin D was extremely variable. Mitomycin C, cyclophosphamide and HN2 all produced regression of Vx-2 carcinome but "cure" was rarely achieved at dosage tolerated by the normal tissues of the limb. A comparative study was also made of the effect of HN2 introduced intra-arterially followed by tourniquet application ("trapping") and local circulatory arrest. The antitumor effect of this approach compared favorably with active perfusion of the same agent. Radiation therapy was also administered in this tumor system, at varying dosages, as a frame of reference for the results obrained by perfusion. The selective effect of irradiation was generally as good as or better than perfusion with any of the agents utilized in this study. The limitation of dosage of these agents by local tissue tolerance prompted a comparative study of the maximum concentrations of agents that were achieved and the concentrations required to destroy Vx-2 cells in vitro. This is the subject of a subsequent report.