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

J Immunother Emphasis Tumor Immunol. 1995 Oct;18(3):188-95. doi: 10.1097/00002371-199510000-00007.


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, 3, and 6 x 10(6) IU/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 x 10(6) IU/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 dose-dependent and sustained increase in peripheral blood eosinophils and lymphocytes was observed, demonstrating that subcutaneous injections in this low-dose 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy
  • Drug Tolerance
  • Eosinophilia / etiology
  • Female
  • Humans
  • Immunotherapy
  • Injections, Subcutaneous
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / adverse effects
  • Kidney Neoplasms / therapy
  • Lymphocytosis / etiology
  • Male
  • Middle Aged
  • Neoplasms / therapy*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Safety
  • Time Factors


  • Interleukin-2
  • Recombinant Proteins