Growth Inhibitors Rapidly Inactivated by the Host as Potential Antineoplastic Agents in Intra-Arterial Infusion Chemotherapy

Abstract

Certain compounds capable of blocking the growth of cultured animal cells or causing them to lose viability upon prolonged exposure may have no apparent effect upon tumor growth in vivo, if administered by injection at widely spaced intervals, due to rapid inactivation, breakdown or excretion by organs of the mammalian host. Continuous infusion or repetitive infusion at shortly-spaced intervals of compounds of this sort into arterial blood supplying the tumor region holds out the prospect of achieving a prolonged localized concentration capable of arresting tumor cell multiplication, while dilution of the inhibitor upon entry into the general circulation and its rapid clearance from the blood via metabolic conversion or excretion prevents accumulation to toxic or immunosuppressive levels in the body of the host. A novel use of bradykinin to induce inhibitor trapping and thereby augment the concentration of inhibitor in the interstitial fluid of the tumor region is described. Examples are presented of compounds potentially useful in this mode of chemotherapy.