Abstract
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, PCO2 , PO2, 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.
Highlights
Osteosarcom a is the m ost frequent prim ary m alignant bone tum or in hum ans
In the treatment of osteogenic sarcoma a distinction can be made between systemic therapy and locoregional treatment
High-dose methotrexate-based systemic chemotherapy is primarily administered in order to eradicate possible micrometastatic disease, and its use was a major breakthrough in the clinical treatm ent of osteosarcom as in the 1970s
Summary
Osteosarcom a is the m ost frequent prim ary m alignant bone tum or in hum ans. Until the 1970s the m ost common approach to the management of localized osteosarcoma was surgical resection, amputation or radiation therapy.[1]. The same experience was found in patients with sarcomas of soft tissue and bone treated w ith cisplatin H ILP.[6] Results of recent publications and of our own experience with a new perfusion m odality, which com bines tum or necrosis factor-a (TNFa ) and melphalan in patients with recurrent melanoma or soft tissue sarcoma, are very prom ising.[7,8] H owe ver, in six of eight evaluable patients with unresectable osteosarcoma of the lower lim b treated w ith T N F a an d m elp halan H IL P, histological evaluation revealed moderate results with
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