POLYETHYLENE-GLYCOL CONJUGATED INTERLEUKIN-2 - CLINICAL AND IMMUNOLOGICAL EFFECTS IN PATIENTS WITH ADVANCED RENAL-CELL CARCINOMA

Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials employed different dose levels: A) 20 x 10(6) l.U./M2 day 1 followed by 12 x 10(6) I.U./M2 days 8, 15, 22; and B) 12 x 10(6) I.U./M2 days 1, 8, 15, 22. Thirty-five patients were entered and 31 were evaluable for response (A - 15/18, B - 16/17). Two of 31 patients had partial responses. Median therapy duration was four weeks (range 1-15), and dose reduction for grade III or IV toxicity was required in 14/35 patients (A-6/18, B-8/17). Toxicity (greater-than-or-equal-to grade III) seen included: hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No differences in response or toxicity between the two schedules were noted. Hematologic changes included lymphocytosis and eosinophilia in the majority of patients. PEG IL-2 given once weekly has significant toxicity, and may produce tumor regression in patients with renal cell carinoma.