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.