A phase I study of recombinant interleukin 2 plus recombinant β-interferon
RL Krigel, KA Padavic-Shaller, AR Rudolph, S Litwin… - Cancer research, 1988 - AACR
RL Krigel, KA Padavic-Shaller, AR Rudolph, S Litwin, M Konrad, EC Bradley, RL Comis
Cancer research, 1988•AACRAbstract Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In
vitro these activities are enhanced by β-interferon (IFN-β). Therefore, we initiated a Phase I
trial with a combination of IL-2 and IFN-β three times weekly. The IFN-β was administered iv
Initially, the IL-2 was administered sc However, neutralizing antibody to the IL-2 developed
in five patients, and the route of administration of the IL-2 was changed to iv Forty-seven
patients were entered on the study. The maximum tolerated doses for the combination given …
vitro these activities are enhanced by β-interferon (IFN-β). Therefore, we initiated a Phase I
trial with a combination of IL-2 and IFN-β three times weekly. The IFN-β was administered iv
Initially, the IL-2 was administered sc However, neutralizing antibody to the IL-2 developed
in five patients, and the route of administration of the IL-2 was changed to iv Forty-seven
patients were entered on the study. The maximum tolerated doses for the combination given …
Abstract
Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In vitro these activities are enhanced by β-interferon (IFN-β). Therefore, we initiated a Phase I trial with a combination of IL-2 and IFN-β three times weekly. The IFN-β 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 × 106 units/m2 of IL-2 and 10 × 106 units/m2 of IFN-β. Dose-limiting toxicities were profound fatigue/decreased performance status, anorexia/weight loss, depression, and arthralgias. Hypotension, exfoliative skin rash, thrombocytopenia, diarrhea, temperature >40.6°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 × 106 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 γ-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 γ-interferon are induced by this therapy, and (d) IL-2 and IFN-β given three times weekly i.v. is both tolerable and biologically active. The recommended Phase II dose is 5 × 106 units/m2 of IL-2 plus 6 × 106 units/m2 of IFN-β.
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