A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2.
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.
Meyers
F J
FJ
Division of Hematology and Oncology, University of California, Davis Medical Center, Sacramento.
Paradise
C
C
Scudder
S A
SA
Goodman
G
G
Konrad
M
M
D000328:Adult; D000818:Animals; D000906:Antibodies / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D000906:Antibodies; D007376:Interleukin-2; D011994:Recombinant Proteins; C067245:interleukin-2, polyethylene glycol-modified; D011092:Polyethylene Glycols