Rationale for using TNFα and chemotherapy in regional therapy of melanoma

F. Lejeune, D. Liénard, A. Eggermont, H. Schraffordt Koops, F. Rosenkaimer, J. Gérain, J. Klaase, B. Kroon, J. Vanderveken, P. Schmitz

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


Recombinant tumor necrosis factor‐alpha (rTNFα) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNFα is hampered by severe systemic side‐effects. The maximum tolerated dose range from 350 to 500 mg/m2, which is at least 10‐fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNFα in a closed system with acceptable side‐effects. A protocol with a triple‐drug regimen was based on the reported synergism of rTNFα with chemotherapy, with interferon‐y, and with hydperthermia. In melanoma‐in‐transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNFα in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this prtocol is due to a dual targeting: rTNFα activates and electively lyses the tumor endothelial cells while melphalan is mainly cytoxic to the tumor cells. ILP with rTNFα appears to be a useful model for studying the biochemotherapy of cancer in man.

Original languageEnglish
Pages (from-to)52-61
Number of pages10
JournalJournal of Cellular Biochemistry
Issue number1
Publication statusPublished - Sept 1994
Externally publishedYes


  • interferon‐γ
  • isolation perfusion
  • melanoma
  • melphalan
  • TNFα


Dive into the research topics of 'Rationale for using TNFα and chemotherapy in regional therapy of melanoma'. Together they form a unique fingerprint.

Cite this