TY - JOUR
T1 - Isolated limb perfusion with TNFα and melphalan in a rat osteosarcoma model
T2 - A new anti-tumour approach
AU - Manusama, Eric R.
AU - Stavast, Jeroen
AU - Durante, Nicola M.C.
AU - Marquet, Richard L.
AU - Eggermont, Alexander M.M.
N1 - Funding Information:
This work was financed in part by the Dutch Cancer Society (Grant DDHK 93-659). We acknowledge Boehringer Ingelheim GmbH for generously providing TNFct.
PY - 1996
Y1 - 1996
N2 - 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 mere 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.
AB - 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 mere 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.
KW - Chemotherapy
KW - Oncology
KW - Osteosarcoma
KW - TNFα
UR - http://www.scopus.com/inward/record.url?scp=0029963270&partnerID=8YFLogxK
U2 - 10.1016/S0748-7983(96)90671-X
DO - 10.1016/S0748-7983(96)90671-X
M3 - Article
C2 - 8608832
AN - SCOPUS:0029963270
SN - 0748-7983
VL - 22
SP - 152
EP - 157
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 2
ER -