Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma.

摘要: Patients with advanced renal cell carcinoma were treated in a Phase I trial escalating doses of recombinant human interleukin-12 (rHuIL-12) given on days 1, 8, and 15 each 28-day cycle. Treatment the initial dose scheme consisted fixed levels 0.1, 0.5, 1.0 microg/kg to cohorts composed three or six patients. On basis toxicity profile, second (up-titration) was undertaken wherein rHuIL-12 escalated for patient from week 1 2, target 3 thereafter; cohort 0.75, 1.0, 1.25, 1.5 microg/kg. Fifty-one patients treated: 32 (63%) had prior cytokine therapy 19 (37%) received no systemic therapy. The maximum tolerated Dose-limiting toxicities included increase transaminase concentration, pulmonary toxicity, leukopenia. most severe occurred first injection milder upon further treatment. With up-titration scheme, reached at microg/kg, dose-limiting an serum levels. At IL-12 increased mean peak level 706 pg/ml. Serum IFN-gamma about 200 pg/ml 24 h after maintenance best responses as follows: one complete response, 34 stable, 14 showed progression, inevaluable. In conclusion, relatively well when administered by s.c. injection. recommended according schedule (microg/kg) II trials cycle 0.1 (day 1), 0.5 8), 1.25 15); 2 onwards, 1.25. initiated previously untreated melanoma.