Background: Kaposi’s sarcoma (KS) is more likely to occur with aggressive features in advanced AIDS. Chronic cytotoxic chemotherapy is often required for control, but cumulative toxicity frequently constrains therapeutic prospects. Relatively non-toxic, antiangiogenic approaches are thus of interest. We have investigated Interleukin-12 (IL-12) in less advanced KS, and this agent appears to be active and well tolerated in long-term dosing. Preclinical evidence suggests that combined cytotoxic and antiangiogenic therapies may have synergistic effects.

Methods: Phase 2 trial of liposomal doxorubicin (20 mg/m² IV every 3 wks) with IL-12 (300 ng/kg SQ BIW) for 18 wks followed by maintenance IL-12 (500 ng/kg twice wkly) to assess the response rate and progression-free survival and toxicity.

Results: Twenty-six (26) patients (pts) with advanced KS have enrolled. Pt characteristics are male 96%; median (range) age = 37 (25–55); performance status = 80 (40–90); CD4 = 142 (14–760); log₁₀ HIV = 2.37 (1.69–5.73). Poor prognosis = 23 (extensive cutaneous and/or visceral involvement = 20). Of 24 evaluable pts to date, the overall response rate (RR) is 83% (95% CI = 63%–95%). Progression was noted in 2 pts during the combined therapy and in 2 relative to criteria reached for partial response during IL-12 maintenance. At the median potential follow-up time of 1 year, the probability of being progression free is 75%. Of 135 cycles of combined therapy, ANC £ 500 cells/mm³ in 10 (7%) cycles; grade ≥ 3 SGOT elevations on 9 (7%) cycles. Of 100 4-wk cycles of IL-12 maintenance administered, 4 (4%) were complicated by grade 4 ANC and 1 by grade 4 hemolysis. Two (2) pts with profoundly advanced HIV had non-neutropenic septic episodes thought unrelated to the treatment. There were no episodes of febrile neutropenia.

Conclusions: The high RR may suggest therapeutic synergy, and maintenance with single agent IL-12 appears feasible. Accrual continues.