A total of 29 patients with advanced
malignancy were treated with recombinant
interferon gamma (rIFN gamma, specific activity = 2.10(7) units/mg, purity greater than 95%) given by intravenous bolus at doses escalating from 0.01 mg/m2 to 5 mg/m2 (2 x 10(5) - 10(8) IU/m2) in nine successive steps (at least 3 patients/step).
Injections of rIFN gamma 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 rIFN gamma was not detected. One partial clinical response was observed in a patient receiving 2 mg/m2. During rIFN gamma
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%. rIFN gamma appears as a well-tolerated and promising therapeutic agent with toxicities and mode of action probably distinct from IFN alpha and beta.