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Related Experiment Videos

Tumour necrosis factor: clinical relevance.

A L Jones1, P Selby

  • 1Section of Medicine, Royal Marsden Hospital, Sutton, Surrey UK.

Cancer Surveys
|January 1, 1989
PubMed
Summary

Tumour necrosis factor (TNF) shows limited anticancer effects in humans at safe doses, causing side effects like hypotension and liver damage. Further research will explore combining TNF with other agents for cancer treatment.

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Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Tumour necrosis factor (TNF) exhibits anticancer properties in preclinical models.
  • Clinical investigation of TNF as a human cancer therapeutic is warranted.

Purpose of the Study:

  • To evaluate the therapeutic potential and safety of TNF in human cancer patients.
  • To determine the maximum tolerated dose (MTD) of TNF and associated toxicities.

Main Methods:

  • Administered escalating doses of TNF (400-800 micrograms ng/m2) to human cancer patients.
  • Monitored for adverse events, including hypotension and hepatic damage.
  • Measured serum TNF concentrations to correlate with clinical effects.

Main Results:

  • The MTD of TNF was established at 400-800 micrograms ng/m2 due to dose-limiting toxicities (hypotension, hepatic damage).
  • No consistent anticancer effects were observed at the established safe doses.
  • Achieved serum TNF concentrations were lower than those effective in murine tumor models.

Conclusions:

  • Single-agent TNF therapy is unlikely to be effective for human cancer treatment at currently tolerable doses.
  • Future strategies may involve combination therapies with TNF and other agents.
  • TNF's role as a mediator of inflammation, shock, cachexia, and organ dysfunction is further clarified.

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