title: Isolated limb perfusion with TNF-alpha and melphalan in locally advanced soft tissue sarcomas of the extremities.
abstract: Limb-sparing surgery has become all the more important in soft tissue sarcoma (STS) of the extremities since we learned that amputation does not improve survival of these patients. In bulky tumours, however, preoperative strategies to reduce tumour size are then required. Isolated limb perfusion (ILP) with tumour necrosis factor (TNF) has been developed as a biochemotherapeutic therapy to act both on the tumour-associated vasculature and on the tumour itself. It has shown to be a very potent treatment modality, as in early reports response rates were around 80%. Limb salvage could then be achieved in a quite similar percentage. Many confirmatory studies have been performed since, with consistent results even in patients with multiple tumours, after extensive radiotherapy or with metastatic disease, all at the cost of very limited toxicity. This chapter gives an overview of the ILP studies performed in patients with soft tissue limb sarcoma, discusses the mechanism of TNF-mediated vasculotoxic effects on tumour vasculature, and places TNF-based ILP in the multimodality treatment of these patients with extensive STS of the extremities.
authors.affiliation: Department of Surgical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, P.O. Box 5201, 3008 AE Rotterdam, The Netherlands.
authors.forename: Dirk J G
authors.initials: DJ
authors.lastname: Grünhagen
authors.forename: Johannes H W
authors.initials: JH
authors.lastname: de Wilt
authors.forename: Albertus N
authors.initials: AN
authors.lastname: van Geel
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D005121:Extremities / Q000473:pathology*; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage*; D012509:Sarcoma / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan