Hyperthermic Isolated Limb Perfusion with TNF α and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-α (TNFα ) and cisplatin for the management of osteosarcoma was studied in the canine model. Methods. During seven perfusions in six healthy mongrel dogs (weight 32±2 kg) technical aspects of HILP under mild hyperthermia (39– 40℃) were studied. In five experiments HILP was performed with TNFα alone (0.5 mg/l extremity volume), and in two experiments TNFα was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFα and total cisplatin concentrations were determined. Results. Perfusion conditions (pH, PCO(2) , PO(2), flow and pressure) remained within physiological ranges.Three dogs died within 24 h despite a sublethal systemic concentration of TNFα that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb. Conclusions. This feasibility study in healthy dogs demonstrated that HILP with TNFα and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFα and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma.