AEGiS-10CROI: Preliminary Results of Combination Liposomal Doxorubicin and Interleukin-12 Followed by Chronic IL-12 Maintenance Therapy in Advanced AIDS-related Kaposi's Sarcoma.

10th Conference on Retroviruses and Opportunistic Infections


Boston, MA USA - February 10 -14, 2003

Print this Article


Preliminary Results of Combination Liposomal Doxorubicin and Interleukin-12 Followed by Chronic IL-12 Maintenance Therapy in Advanced AIDS-related Kaposi's Sarcoma.

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 816
Little RF, Aleman K, Merced, Wyvill K, Catanzaro A, Maldarelli F, Steinberg SM, Yarchoan R; Natl Cancer Inst, Bethesda, MD

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.

Keywords: AEGIS, Sarcoma, Kaposi, Doxorubicin, Antibiotics, Anthracycline, Acquired Immunodeficiency Syndrome, Interleukin-12, HIV, Skin Neoplasms, HIV-2, HIV-1, Anti-HIV Agents, Commonwealth of Independent States, Male, HumanKWDaegis,sarcoma,kaposi,doxorubicin,antibiotics,anthracycline,acquiredimmunodeficiencysyndrome,interleukin-12,hiv,skinneoplasms,hiv-2,hiv-1,anti-hivagents,commonwealthofindependentstates,male,human

030210
816

Copyright © 2003 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.