Feasibility and pharmacokinetics of continuous subcutaneous infusion of low-dose interferon-gamma: a pilot study

Continuous subcutaneous infusion of interferon-gamma was carried out in an attempt to improve the therapeutic efficacy of the agent, one of the most potent immunomodulatory cytokines. Seven patients with renal cell carcinoma underwent the therapy using battery-powered micro-infusion pumps. In four patients, recombinant human interferon-gamma, 15 x 10(6) JRU (Japan Reference Unit)/body, was administered subcutaneously and continuously for five days. The therapy was repeated without interruption up to three times in four patients, including one for whom a single course of five-day therapy had been given three months previously. The major side effects were fever, anorexia, general malaise and local skin reaction. Discontinuation of the therapy was necessary in two patients, one in single five-day therapy and the other in repeated therapy, due to generalized skin eruption and general malaise, respectively. Serum interferon-gamma levels, as determined by radioimmunoassay, increased gradually and reached 20-30 IU/ml on day 4 or 5. Among patients who received two or three courses of therapy, the interferon-gamma levels showed high inter-individual differences after day 6. The levels gradually fell after the therapy terminated with a half-life of about 2 days. No clinical response was observed. Our data suggest that interferon-gamma can be administered by continuous subcutaneous infusion, and warrants further study.