Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumour approach.
Isolated limb perfusion (ILP) with TNF alpha, IFN gamma 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, TNF alpha alone, melphalan alone or their combination. Almost all rats, treated with a sham ILP or a perfusion with 40 micrograms melphalan, showed progressive disease (PD) (6/6 and 5/6). After perfusion with 50 micrograms TNF alpha 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 TNF alpha and melphalan. The discrepancy with the in vitro sensitivity of ROS-1 indicates that indirect effects are important in this tumour model.
Manusama
E R
ER
Department of Surgery, University Hospital Rotterdam/dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Stavast
J
J
Durante
N M
NM
Marquet
R L
RL
Eggermont
A M
AM
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy / Q000628:therapy*; D010477:Perfusion / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan