Isolated limb perfusion with melphalan and TNF-alpha in the treatment of extremity sarcoma.
Isolated limb perfusion (ILP) with chemotherapy alone has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor necrosis factor-alpha (TNF-alpha) to this treatment approach contributed to a major step forward in the treatment of locally advanced extremity soft tissue sarcoma (STS). High response rates and limb salvage rates have been reported in multicenter trials, which combined ILP with TNF-alpha plus melphalan, which resulted in the approval of TNF-alpha for this indication in Europe in 1998. Subsequently a series of confirmatory single institution reports on the efficacy of the procedure have now been published. TNF-alpha has an early and a late effect; it enhances tumor-selective drug uptake during the perfusion and plays an essential role in the subsequent selective destruction of the tumor vasculature. These effects result in a high response rate in high-grade soft tissue sarcomas. This induction therapy thus allows for resection of tumor remnants some 3 months after ILP and thus avoidance of limb amputation. TNF-alpha-based ILP is a well-established treatment to avoid amputations. It represents an important example of tumor vascularity-modulating combination therapy and should be offered in large volume tertiary referral centers.
Verhoef
Cornelis
C
Department of Surgical Oncology, ErasmusMC-Daniel den Hoed Cancer Center, 310 Groene Hilledijk, 3075 EA, Rotterdam, The Netherlands. c.verhoef@erasmusmc.nl
de Wilt
Johannes H W
JH
Grünhagen
Dirk J
DJ
van Geel
Albertus N
AN
ten Hagen
Timo L M
TL
Eggermont
Alexander M M
AM
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion; D004359:Drug Therapy, Combination; D005121:Extremities / Q000098:blood supply / Q000601:surgery; D005260:Female; D006801:Humans; D023821:Limb Salvage; D008558:Melphalan / Q000008:administration & dosage*; D012509:Sarcoma / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan