Isolated limb perfusion with TNFα and melphalan in a rat osteosarcoma model: a new anti-tumour approach

Isolated limb perfusion (ILP) with TNFα, IFNγ and melphalan causes impressive tumour reduction in patients with irresectable soft tissue sarcomas with a high limb salvage rate. Since this therapy could be of value in patients with progressive osteosarcoma, we performed a study in an osteosarcoma tumour model in the rat. The ROS-1 osteosarcoma was implanted s.c. in the hind leg of WAG rats. Rats were divided in four groups: rats that underwent ILP with perfusate alone, TNFα alone, melphalan alone or their combination. Almost all rats, treated with a sham ILP or a perfusion with 40 μg melphalan, showed progressive disease (PD) (6/6 and 5/6). After perfusion with 50 μg TNFα alone a varied response was observed: 2/6 PD, 2/6 no change (NC) and 2/6 a complete remission (CR). After combined perfusion: 3/6 rats had a partial remission and 3/6 a CR. The best and most consistent responses are obtained by combining TNFα and melphalan. The discrepancy with the in vitro sensitivity of ROS-1 indicates that indirect effects are important in this tumour model.