H ypertherm ic isolated lim b perfusion with TNFa and cisplatin in the treatm ent of osteosarcom a of the extrem ities: a feasibility stu dy in healthy dogs

Abstract Pur pose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-a (TNFa ) and cisplatin for the m anagement of osteosarcoma was studied in the canine m odel. M ethods. During seven perfusions in six healthy mongrel dogs (weight 32±2 kg) technical aspects of HILP under mild hyperthermia (39± 40Ê C) were studied. In ® ve experim ents HILP was perform ed with TNFa alone (0.5 mg/l extremity volume), and in two experiments TNFa was combined with cisplatin (25 mg/l extrem ity volume). During the perfusions physiological parameters were m onitored and TNFa and total cisplatin concentrations were determined. Results. Perfusion conditions (pH, PCO 2 , PO 2 ,¯ow and pressure) rem ained within physiological ranges. Three dogs died within 24 h despite a sublethal systemic concentration of TN Fa 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 dem onstrated that HILP with TNFa and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFa 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. Key words: Osteosa rcom a of the extrem ity, hyperther m ic isolation, lim b perfusion, chem otherapy, com bination therapy, dog