Isolated Limb Perfusion with Melphalan and TNF-α in the Treatment of Extremity Sarcoma

Abstract

Opinion statement 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-α) 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-α plus melphalan, which resulted in the approval of TNF-α 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-α 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-α-based ILP is a well-established treatment to avoid amputations. It represents an important example of tumor vasculatory-modulating combination therapy and should be offered in large volume tertiary referral centers.

Hyperthermic isolated limb perfusion for recurrent melanomas and soft tissue sarcomas: Feasibility and reproducibility in a multi-institutional Hellenic collaborative study

“…Limb salvage, the primary objective of this treatment reached 92% in our series that is comparable with rates reported in the literature demonstrating high efficacy of TM-HILP in unresectable in-transit melanoma (14). Overall response rates reported in the literature for unresectable soft tissue sarcomas are generally lower compared with melanomas and vary from 53 to 91% (15). Complete and partial response rates constitute ~20 and 50% of the total, respectively and limb salvage ranges between 58 and 89% in several single centre studies (15,16).…”

“…Overall response rates reported in the literature for unresectable soft tissue sarcomas are generally lower compared with melanomas and vary from 53 to 91% (15). Complete and partial response rates constitute ~20 and 50% of the total, respectively and limb salvage ranges between 58 and 89% in several single centre studies (15,16). Due to small number of patients meaningful comparison of our results with those reported in the literature is not feasible.…”

Progranulin: A Proteolytically Processed Protein at the Crossroads of Inflammation and Neurodegeneration

“…TNF-␣ was first discovered as a humoral factor that caused rapid hemorrhagic necrosis of experimental tumors. It is cytotoxic to several tumor cell lines in vitro, increases endothelial permeability, may stimulate an antitumor immune response, and is in clinical use for immunotherapy of limb sarcomas (81). By overexpressing progranulin, a presumed TNF-␣ antagonist, tumors may escape TNF-␣ toxicity.…”

Perfusión aislada de extremidades en sarcomas: experiencia con melfalán como agente único quimioterapéutico en el Instituto Nacional de Cancerología (INC) de Colombia

“…Por otro lado, no se debe utilizar la actinomicina D junto con el TNF debido a la toxicidad en los tejidos normales 34 . La PEA con sólo quimioterapia no es tan eficaz como la PEA con quimioterapia y TNF-α 35 . El TNF-α tiene tanto un efecto temprano como tardío, potencializando la captación selectiva del melfalán por parte del tumor unas 3-6 veces durante la perfusión y logrando la destrucción selectiva de la vasculatura tumoral.…”