A PHASE-I TRIAL WITH RECOMBINANT INTERFERON-GAMMA (ROUSSEL UCLAF) IN ADVANCED CANCER-PATIENTS

A total of 29 patients with advanced malignancy were treated with recombinant interferon γ (rIFNγ, specific activity = 2.107 units/mg, purity >95%) given by intravenous bolus at doses escalating from 0.01 mg/m2 to 5 mg/m2 (2 × 105-108 IU/m2) in nine successive steps (at least 3 patients/step). Injections of rIFNγ were repeated every 72 h for 15 days. Toxicity was evaluated according to the WHO scale. Fever and chills occurred in all patients treated without clear dose effect. Nausea and vomiting appeared at the fifth dose level and their frequency seemed to be dose-related. Cardiovascular side-effects (first-degree atrioventricular reversible block) were observed at the 2 mg/m2 and 5 mg/m2 levels (3 patients). Hematological toxicities were mild (2 grade 1 and 1 grade II cases of granulocytopenia). Minor biological modifications included a transitory rise in hepatic enzymes (12 patients), which correlated with the presence of liver metastasis. Hypocholesterolemia was observed in 18 patients. The appearance of antibodies against rIFNγ was not detected. One partial clinical response was observed in a patient receiving 2 mg/m2. During rIFNγ therapy this patient had the highest scores in this series for peripheral T lymphocytes with an activated phenotype (HLA DR+, TAC+) = 15% and for natural killer (NK) cells (NKH1, Leu19+) = 17%. rIFNγ appears as a well-tolerated and promising therapeutic agent with toxicities and mode of action probably distinct from IFNα and β. © 1990 Springer-Verlag.