Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination with interferon-gamma and melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial.

Abstract

ILP with TNF, IFN, and melphalan is a safe and highly effective induction biochemotherapy procedure that can achieve limb salvage in patients with nonresectable extremity STS. TNF is an active anticancer drug in humans in the setting of ILP.

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

“…For this reason, FasL can be administered to patients only regionally. Regional administration of relatively high doses of TNF in combination with chemotherapeutic drugs has produced high-response rates in patients with advanced limb tumors (7)(8)(9), as well as regression of primary and metastatic tumors confined to the liver (10). These results are of particular interest, because they show that, in principle, the antitumor effects of FasL may be exploited therapeutically in humans with greater success if sufficient dose levels can be attained locally, and if the organism can be exempted from the systemic toxic effects.…”

Fifty Tumor Necrosis Factor?Based Isolated Limb Perfusions for Limb Salvage in Patients Older Than 75 Years With Limb-Threatening Soft Tissue Sarcomas and Other Extremity Tumors

“…However, in an isolated perfusion setting, it can be used very safely and is extremely efficient in inducing tumor responses when combined with cytostatic agents. We have demonstrated that this extremely potent synergy is based on the selective vasodestruction of the tumor-associated vasculature, 5,17 as well as on the greatly enhanced uptake of melphalan or any other chemotherapeutic drug in the tumor when combined with TNF in the ILP setting. 18,19 Safe administration of TNF is guaranteed because we use continuous leakage monitoring and adequate hydration of patients.…”

“…In contrast to the inefficacy of ILP with melphalan alone in the management of irresectable extremity STS, with response rates of only 10% to 35%, 3,4 the introduction of tumor necrosis factor-␣ (TNF) in combination with melphalan in ILP has been reported in a European multicenter trial; it resulted in response rates Ͼ80% and limb-salvage rates Ͼ70% in STS. 5,6 These results led to the approval of TNF in Europe. 7 Also, in the management of in-transit metastases, TNF seems to improve complete response (CR) rates, 8 especially in patients with bulky tumors and in patients whose previous ILP with melphalan alone failed, as has been demonstrated by reports from the Surgery Branch of the National Cancer Institute in the United States.…”

Systemic Therapy in Soft Tissue Sarcomas: Past, Present and Future

“…TNF-alpha increases the vascular permeability of cytotoxic drugs. Eggermont A.M et al [8] demonstrated an overall response rates of 76% and a limb salvage rate of 82% with rhTNFalpha along with IFN gamma and melphalan. Edema, skin erythema and blistering were major postprocedural complications.…”