Phase I Study of a Combination of Recombinant Tumor Necrosis Factor-α and Recombinant Interferon-γ in Cancer Patients

ABSTRACT Combinations of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-α (rTNF-α) and rIFN-γ combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-α and rIFN-γ by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks. The dose levels were 5/5, 10/5, 10/10, 25/10, 25/25, 50/25, 50/50, 75/50, and 75/75 μg/m2 per day of rTNF-α/ rIFN-γ. A minimum of 2 patients were entered sequentially at each dose level. If the first 2-week cycle of therapy was well tolerated, the dose was increased to the next highest dose level during the second 2-week cycle. Fever, chills, and fatigue were observed at all doses. Severity of symptoms corresponded to increasing dose levels. Although TNF is identical to a molecule known as "cachectin," the vast majority of our patients did not lose weight while on study. However, alterations i...