A phase I study of recombinant interleukin 2 plus recombinant beta-interferon.

Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In vitro these activities are enhanced by beta-interferon (IFN-beta). Therefore, we initiated a Phase I trial with a combination of IL-2 and IFN-beta three times weekly. The IFN-beta was administered i.v. Initially, the IL-2 was administered s.c. However, neutralizing antibody to the IL-2 developed in five patients, and the route of administration of the IL-2 was changed to i.v. Forty-seven patients were entered on the study. The maximum tolerated doses for the combination given i.v. were 5 x 10(6) units/m2 of IL-2 and 10 x 10(6) units/m2 of IFN-beta. Dose-limiting toxicities were profound fatigue/decreased performance status, anorexia/weight loss, depression, and arthralgias. Hypotension, exfoliative skin rash, thrombocytopenia, diarrhea, temperature greater than 40.6 degrees C, and peripheral edema were rarely dose limiting. Thirty-two patients were evaluable for response. After 4 weeks of treatment, 21 patients had stable disease, three patients had a minor response, and one patient had a partial response. Significant lymphokine-activated killer cell (LAK) activity was seen in seven patients (22%) and required 5 x 10(6) units/m2 of IL-2. Those who had progressive disease had significantly less LAK activity than those with either stable disease or a response. This therapy also induced more than 60 units/ml of endogenous gamma-interferon 4 h after the i.v. IL-2 administration. This study demonstrates that (a) intermittent i.v. bolus IL-2 therapy can generate LAK activity, (b) LAK activity may be associated with an antitumor response, (c) significant levels of gamma-interferon are induced by this therapy, and (d) IL-2 and IFN-beta given three times weekly i.v. is both tolerable and biologically active. The recommended Phase II dose is 5 x 10(6) units/m2 of IL-2 plus 6 x 10(6) units/m2 of IFN-beta.