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Interleukin 12 (IL-12) Appears to Be Active in AIDS-Associated Kaposi's Sarcoma (KS): Early Results of a Pilot Study R. F. LITTLE*1, J. M. PLUDA1, K. WYVILL1, J. LIETZAU1, G. SHEARER1, G. TOSATO2, E. FEIGAL1, C. CHOUGNET1, K. FOWKE1, and R. YARCHOAN1.
1NCI and 2FDA, Bethesda, MD Background: IL-12 inhibits angiogenesis by stimulating interferon-g (IFN-gg) production with subsequent induction of inducible protein-10 (IP-10). IL-12 also modulates TH1 cell development, restores HIV-specific T-cell immune responses, and enhances cytotoxic and natural killer T-cells.
Methods: Eligible pts took stable antiviral therapy for > 4 wks prior to entry; had no visceral KS or active opportunistic infections; and received no KS therapy within 3 wks of entry. Successive cohorts received escalating doses (ng/kg) of 100 (5 pts), 300 (6 pts), and 500 (5 pts) administered subcutaneously twice weekly.
Results: The median (range) entry CD4 cell count and HIV viral load was 306/mm3 (17-602) and 1601 copies/mL (<200-157,000), respectively. 15/16 pts had ACTG staging poor risk features. 15/16 pts had received prior KS treatment. G-CSF responsive leukopenia developed in 6 pts. 2 pts withdrew for IL-12-related toxicity: 1 for reversible transaminitis and 1 for hemolytic anemia. A self-limiting flu-like syndrome occurred frequently with initial doses of IL-12. CD4 cells counts and viral load were stable during treatment. No responses were seen in the 4 evaluable patients receiving 100 ng/kg. 5/5 and 3/5 evaluable pts receiving 300 and 500 ng/kg , respectively, achieved a partial response (80% response rate, 95% CI= 55-100%). Of these, 6 had prior KS progression on HAART. With a median follow-up of 46 weeks, no responding pts have had KS progression. Enrollment at higher doses continues.
Conclusion: IL-12 appears to be well tolerated in KS at current doses. Primary toxicities include reversible neutropenia, hepatotoxicity, and self-limiting constitutional symptoms. Among pts at the 300 and 500 ng/kg dose levels, an 80% long-lasting partial response rate was achieved.
Key Words: HAART, Interleukin-12, Kaposi's sarcoma
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