Phase I study of prolonged low-dose subcutaneous recombinant interleukin-2 (il-2) in patients with advanced cancer

The present trial was designed to assess the feasibility of subcutaneous low-dose interleukin-2 (IL-2) given for 3 months in an outpatient setting. Twenty patients with advanced cancers (16 metastatic renal cell carcinoma) were included in this phase I study at the following three dose levels: 1,e, and 6 × 10⁶IU/day (groups of 6, 6, and 8 patients, respectively), IL-2 was administered once daily 6 days a week for 12 weeks. Complete therapy was achieved in 13 of 20 patients, whereas 5 of 20 received at least 5 weeks of IL-2. Minor dose-dependent toxicities were observed including fatigue, transient grade 2–3 fever (11 of 18), and grade 1–2 digestive disorders (6 of 18) without significant biologic modifications but two cases of hypothyroidism. Doses were decreased from 6 to 3 × 10⁶IU/day in one patient (fever and allergic edema). All patients developed transient subcutaneous nodules at the injection sites. These side effects never required hospitalization nor discontinuation of therapy. A dosedependent and sustained increase in periopheral blood eosinophils and lymphocytes was observed, demonstrating that subcutaneous injections in this lowdose range could have similar biologic effects to those achieved with more intensive schedules. Because it is safe, practicable, and low in cost, we conclude that s.c. low-dose IL-2 could be useful for the design of immunomodulation trials with potential new application fields.