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Tumor necrosis factor (TNF) is a protein produced by activated macrophages (immune system cells) in response to circulating toxins. One important physiological effect of TNF is to produce necrosis (tissue death) of experimentally induced tumors. With the cloning of the gene for human TNF, large quantities of the substance have become available, and experiments have been carried out investigating its possible use as an anti-cancer agent. The authors discuss previous studies of TNF performed by themselves and others. Complications of this treatment regimen, especially alterations in the levels of liver enzymes, were reported. Patients developed hyperbilirubinemia (high blood levels of bilirubin, a liver bile constituent), as well as jaundice induced by inhibition of bile flow (cholestatic jaundice). The possibility that these effects were caused by spread of the cancer to the liver was ruled out by noting the abatement of liver symptoms with cessation of TNF treatment. Liver biopsies were not performed, so no biochemical or microscopic analysis of liver tissue was possible in these cases. The observations suggest that TNF has direct pathogenic effects on the liver, and the hypothesis is put forward that disruptions in liver function seen in conditions where TNF levels would be increased (following viral infections, in liver failure, and in chronic liver disease) may be directly attributable to TNF. (Consumer Summary produced by Reliance Medical Information, Inc.)

Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival. [ABSTRACT FROM AUTHOR]

A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan. [ABSTRACT FROM AUTHOR]