High dose tumor necrosis factor-? and melphalan administered via isolated limb perfusion for advanced limb soft tissue sarcoma results in a >90% response rate and limb preservation

Abstract

The combination of high dose rTNF-alpha and melphalan given via ILP appears to be effective in patients with advanced soft tissue sarcoma confined to the limb, achieving a high response rate and limb preservation.

Gene delivery from the E3 region of replicating human adenovirus: evaluation of the E3B region

“…Several laboratories have recently reported, however, promising data utilizing TNF in limb perfusion studies which limit systemic exposure. 22,[26][27][28][29][30][31][32][33] Consequently, coupling TNF expression to a replicationselective Ad should limit its expression to the infected tumor, reducing systemic toxicity and increasing its therapeutic effectiveness alone or in combination therapies.…”

Hyperthermic Isolated Limb Perfusion for Extremity Sarcomas

“…In early studies in sarcoma patients, 8,9 the overall response rates were fairly low -approximately 20%-35%, with 11% CR. However, more recent studies [10][11][12][13] show improved responses, with up to 37% CR and 57% PR and with limb salvage rates of 80%-90%.…”

“…11,16 Eggermont et al 16 published one of the largest series of HILP for soft-tissue sarcomas using TNF and melphalan. Of 246 patients, pathologic CRs were seen in 28% and PRs in 47%.…”

“…Interferon gamma has also been used in addition to TNF and melphalan and appears to add no further benefit. 11,17,18 Sarcomas are tumors of mesenchymal origin with a wide range of histologic features. Response to limb perfusion may be better in certain histologies of sarcomas than others.…”

In Vitro Cytotoxicity of Recombinant Human-TNF-.ALPHA. and Actinomycin D on Canine Normal and Tumor Cells.

“…To achieve the effective dose of TNF in tumors without these side effects, TNF should be administered intratumorally [10] or through isolation perfusion [8,16].…”