[A phase I study of recombinant interleukin 2 (S6820)]

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Refractory malignancies present significant treatment challenges.
• Interleukin 2 (IL2) is a cytokine with potential anti-cancer properties.
• Phase I studies are crucial for determining safe and effective dosing of novel therapeutics.

Purpose of the Study:

• To evaluate the safety and tolerability of recombinant human interleukin 2 (IL2) in patients with refractory malignancies.
• To identify the maximum tolerated dose (MTD) and dose-limiting toxicities of IL2.
• To assess the immunomodulatory effects of IL2, including natural killer (NK) and lymphokine-activated killer (LAK) cell activity.

Main Methods:

• A cooperative phase I clinical study involving 40 patients with refractory malignancies.
• Intravenous administration of IL2 across a range of doses (1 x 10^4 to 3.3 x 10^6 U/day) and subcutaneous administration at 1 x 10^6 U/day for 5 days.
• Monitoring for dose-related toxicities, including fever, gastrointestinal disturbances, rash, arthralgia, eosinophilia, hepatotoxicity, and hypotension.
• Assessing changes in NK and LAK cell activity at different IL2 dose levels.

Main Results:

• Toxicity was dose-dependent, with common side effects including fever, chills, and gastrointestinal issues.
• Severe hypotension occurred at the highest dose (3.3 x 10^6 U/day), necessitating treatment withdrawal in one case.
• Enhanced NK and LAK cell activity was observed at doses of 1 x 10^6 U/day and higher.
• All observed toxicities resolved after IL2 administration ceased.

Conclusions:

• The optimal dose of recombinant human IL2 for further investigation appears to be 1 x 10^6 U/day.
• This dose demonstrated immunomodulatory effects with manageable toxicity.
• Findings support the design of a phase 2 study to further evaluate IL2 efficacy in refractory malignancies.