Technology insight: Utility of TNF-α-based isolated limb perfusion to avoid amputation of irresectable tumors of the extremities

Dirk J. Grünhagen, Johannes H.W. de Wilt, Timo L.M. ten Hagen, Alexander M.M. Eggermont

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenpeer review

81 Citaten (Scopus)


Isolated limb perfusion (ILP) with melphalan is effective in the treatment of small multiple melanoma intransit metastases and is utilized widely for this indication. The treatment is much less effective against bulky melanoma metastases and has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor-necrosis factor-α (TNF-α) to this treatment approach has changed the situation dramatically. High response rates and limb-salvage rates have been reported in multicenter trials that combined ILP with TNF-α plus melphalan; these trials resulted in the approval of TNF-α for bulky melanoma metastases and soft tissue sarcomas in Europe in 1998. Subsequently, many doctors working in European centers have been trained, and a series of confirmatory reports from single institutions have now been published regarding the efficacy of the procedure. 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 bulky tumors, soft tissue sarcomas, bulky melanomas, and various other tumor types. This induction therapy therefore allows tumor remnants to be resected some 3 months after ILP thus avoiding limb amputation. TNF-α-based ILP is a well-established treatment that aims to avoid amputations regardless of the tumor size and type. It represents an important example of combination therapy that modulates the tumor vasculature and should be offered in high-volume tertiary referral centers.

Originele taal-2Engels
Pagina's (van-tot)94-103
Aantal pagina's10
TijdschriftNature Clinical Practice Oncology
Nummer van het tijdschrift2
StatusGepubliceerd - feb. 2006
Extern gepubliceerdJa


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