High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma.

Abstract

This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration. Tumor responses can be evidenced in melanoma and sarcoma. Furthermore, combination of rTNF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy with melphalan alone.

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.…”

Molecular design of hybrid tumour necrosis factor-alpha. II: The molecular size of polyethylene glycol-modified tumour necrosis factor-alpha affects its anti-tumour potency

“…Furthermore, the therapeutic efficacy of TNF-a alone has not lived up to expectations (Creaven et al, 1987;Kimura et al, 1987). Therefore, cancer therapy with TNF-a has only been proceeded by intratumoral administration in combination with other anti-tumour drugs (Pfreundschuh et al, 1989;Lienard et al, 1992). A single intravenous administration of PEG12 000-TNF-a Fr.3 or MPEG-TNF-cx alone induced marked anti-tumour effects without TNF-a-mediated sideeffects.…”

“…More recently, evidence has been accumulated that the adverse side-effects of TNF-a are substantially enhanced by its combination with interferon-y and interleukin-2, when systemically administered Yang et al, 1991;Schiller et al, 1992). Nowadays, the clinical application of TNF-a is limited to intratumoral administration, and its clinical consequence is unfavourable (Pfreundschuh et al, 1989;Lienard et al, 1992).…”

Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts

“…Furthermore, TNF-a seems to play an important vasodilatory role in host response to septic insults (Tracey et al, 1987), potentially mediated by the release of nitric oxide (NO) from endothelial cells or macrophages (Baudry and Vicaut, 1993;Kilbourn et al, 1990). The combination of TNF-a, melphalan and interferon-y in regional perfusion of human extremity sarcomas and melanomas has resulted in impressive response rates (Vaglini et al, 1994;Lienard et al, 1992), presumably owing to a combined early effect on tumour vasculature and a possible immune enhancement effect of TNF-a (Fraker and Alexander, 1993). A relationship between production of vascular endothelial growth factor (VEGF) and TNF-a cytotoxicity has been demonstrated in vivo, supporting the hypothesis of a vascular effect of TNF-a on tumour tissue (Amikura et al, 1995).…”