A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2

Clin Pharmacol Ther. 1991 Mar;49(3):307-13. doi: 10.1038/clpt.1991.33.


A more soluble formulation of recombinant interleukin-2 with a prolonged half-life would allow alternate routes or schedules of administration and enhance patient comfort. The covalent attachment of polyethylene glycol to recombinant interleukin-2 provides an analog with preclinical data suggesting those desired characteristics while maintaining biologic activity. This is the report of a phase I study in which we sought to determine the maximum tolerated dose of polyethylene glycol interleukin-2, observe biologic activity, and confirm the prolonged half-life in vivo. Sixty-six patients were entered into the study during 19 months. Polyethylene glycol interleukin-2 was administered intravenously once a week over 15 minutes. The maximum tolerated dose was 20 x 10(6) U/M2. The pattern of toxicity was quite similar to that of the parent compound. Four patients had evidence of tumor regression (three partial remission; one minor response). The pharmacokinetic data confirmed a 10- to 20-fold prolongation in half-life compared with recombinant interleukin-2. No neutralizing antibodies were detected. This study provides sufficient impetus for the ongoing phase II studies of polyethylene glycol interleukin-2.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies / analysis
  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Female
  • Humans
  • Injections, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / analogs & derivatives
  • Interleukin-2 / pharmacokinetics*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / pharmacokinetics*
  • Rabbits
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics


  • Antibodies
  • Interleukin-2
  • Recombinant Proteins
  • interleukin-2, polyethylene glycol-modified
  • Polyethylene Glycols