Hyperthermic isolated limb perfusion with TNFalpha and cisplatin in the treatment of osteosarcoma of the extremities: a feasibility study in healthy dogs

Author: Ginkel Robert J. Van   Berlo Charles L. H. Van   Baas Peter C.   Koops Heimen Schraffordt   Stuling Ries Van Groningen B.   Elstrodt Jan   Hoekstra1 Harald J.  

Publisher: Informa Healthcare

ISSN: 1369-1643

Source: Sarcoma, Vol.3, Iss.2, 1999-09, pp. : 89-94

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Abstract

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNFalpha) 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 C) were studied. In five experiments HILP was performed with TNFalpha alone (0.5 mg/l extremity volume), and in two experiments TNFalpha was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFalpha and total cisplatin concentrations were determined. Results. Perfusion conditions (pH, PCO2, PO2, flow and pressure) remained within physiological ranges. Three dogs died within 24h despite a sublethal systemic concentration of TNFalpha 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 TNFalpha and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFalpha 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.

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