Three Schedules of Recombinant Human Interleukin‐2 in the Treatment of Malignancy: Side Effects and Immunologic Effects in Relation to Serum Level

Recombinant human interleukin‐2 (rIL‐2) was administered to 34 patients with advanced malignancy. Three schedules of rIL‐2 administration employed were as follows: (A) 2‐hr iv infusion of 6.7 × 10(*5) U/m(*2)/day (A(1), 6 cases) or 2.2 × 10(*6) U/m(*2)/day (A(2), 8 cases) for five consecutive days; (B) 24‐hr continuous iv infusion of 3.3 × 10(*5) U/m(*2)/day (B(1), 3 cases), 6.7 × 10(*5) U/m(*2)/day (B(2), 7 cases) or 1.1 × 10(*6) U/m(*2)/day (B(3), 5 cases) for 28 consecutive days; and (C) 24‐hr continuous iv infusion of 6.7 × 10(*5) U/m(*2)/day (C, 5 cases) for 5 consecutive days per week for four weeks. The common side effects were fever (79%), eosinophilia (61%), malaise (56%), erythema or rash (50%), chills (38%) and nausea or vomiting (35%), with the dose‐limiting toxicities being hypotension in group A, and renal dysfunction with fluid retention in groups B and C. In the case of 2‐hr iv infusion, rIL‐2 was rapidly cleared from the plasma, with a half life of about 30 min, while in the case of 24‐hr continuous infusion, more than 1 U/ml serum IL‐2 activity was maintained for 14 days in group B(3). Natural killer (NK) and lymphokine‐activated killer (LAK) activities were augmented by rIL‐2 administration in patients of groups A, B(3) and C. In eight patients of group B, NK and LAK activities transiently decreased after rIL‐2 administration, and recovered by day 3. The percentage of IL‐2 receptor and Leu HLA‐DR positive cells reached the peak level on day 7 in group B. In patients of group C, the percentage of Leu HLA‐DR positive cells as well as NK and LAK activities increased upon rIL‐2 administration and decreased during an intermission of two days. However, the percentage of rIL‐2 receptor positive cells increased during the intermission of rIL‐2. The most effective schedule of rIL‐2 administration was considered to be the schedule of group C on the basis of this study.