Hyperthermic isolated limb perfusion with cis-diamminedichloro-platinum. II. An experimental study in dogs with a balloon-occlusion technique for repeated high-dose treatment.

Isolated organ perfusion is attractive for regional high-dose chemotherapy because of its advantage to reduce whole body toxicity. Intraoperative hyperthermic isolated perfusion procedures involving a heart-lung machine have been developed, but repeated treatments carry a high risk of vessel and tissue damage. Therefore, a study of isolated hyperthermic limb perfusion in four dogs was conducted using a balloon-occlusion technique including a hyperthermia unit, two low-flow rotary pumps, a bubble oxygenator, and two polyurethane balloon catheters. After 15 min infusion of cisplatinum the concentrations of serum platinum (Pt) in the isolated limb and in the whole body were measured by atomic absorption spectroscopy. Regional exposure to Pt was more than 10-fold higher than systemic exposure. After 60 min isolated limb perfusion, the area under the curve (AUC) of Pt concentrations in the isolated limb showed values between 767.4 and 1055.6 micrograms/l x 60 min, whereas in the whole body values between 59.8 and 75.9 micrograms/l x 60 min were obtained. Repeated isolated limb perfusions with the balloon-occlusion technique were performed in three dogs without systemic side effects. This model of regional chemotherapy may be useful for preoperative chemotherapy in malignant tumors of the limbs.