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 deal data suggesting those desired characteristics while maintaining biologic activity. This is the report of a phase 1 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 × 106 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 pharmaeokinetic 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.
|Original language||English (US)|
|Number of pages||7|
|Journal||Clinical Pharmacology and Therapeutics|
|State||Published - Mar 1991|
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