HYPERTHERMIC ISOLATED LIMB PERFUSION WITH CIS-DIAMMINEDICHLORO-PLATINUM .2. AN EXPERIMENTAL-STUDY IN DOGS WITH A BALLOON-OCCLUSION TECHNIQUE FOR REPEATED HIGH-DOSE TREATMENT

Isolated organ perfusion is attractive for regional high-dose chemothe rapy because of its advantage to reduce whole body toxicity. Intraoper ative hyperthermic isolated perfusion procedures involving a heart-lun g machine have been developed, but repeated treatments carry a high ri sk of vessel and tissue damage. Therefore, a study of isolated hyperth ermic limb perfusion in four dogs was conducted using a balloon-occlus ion technique including a hyperthermia unit, two low-flow rotary pumps , a bubble oxygenator, and two polyurethane balloon catheters. After 1 5 min infusion of cisplatinum the concentrations of serum platinum (Pt ) in the isolated limb and in the whole body were measured by atomic a bsorption spectroscopy. Regional exposure to Pt was more than 10-fold higher than systemic exposure. After 60 min isolated limb perfusion, t he area under the curve (AUC) of Pt concentrations in the isolated lim b showed values between 767.4 and 1055.6 mu g/l x 60 min, whereas in t he whole body values between 59.8 and 75.9 mu g/l x 60 min were obtain ed. Repeated isolated limb perfusions with the balloon-occlusion techn ique were performed in three dogs without systemic side effects. This model of regional chemotherapy may be useful for preoperative chemothe rapy in malignant tumors of the limbs. (C) 1994 Wiley-Liss, Inc.