Recombinant Alpha-2 Interferon Therapy for Kaposi's Sarcoma Associated with the Acquired Immunodeficiency Syndrome

Abstract

In a randomized prospective study we tested the toxicity and efficacy of recombinant alpha-2 interferon in the treatment of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. High doses (50 X 10(6) U/m2 body surface area, intravenously) or low doses (1 X 10(6) U/m2, subcutaneously) of recombinant alpha-2 interferon were administered to 20 patients for 5 days/wk, every other week, for four treatment cycles. Therapy was well tolerated subjectively and caused only mild hematologic and hepatic toxicity at both dose levels. No consistent or sustained changes were seen in immunologic variables during or after treatment. Six patients with Kaposi's sarcoma, four at high dose and two at low dose, had objective responses (complete or partial) to treatment. However, therapy did not appear to eradicate cytomegalovirus carriage or prevent opportunistic infections related to cytomegalovirus.

Molecular Targets for AIDS Therapy

“…Although the antiretroviral mechanism of interferons is as yet not clear, IFN-o may be clinically useful in several ways. This agent has an in vivo antitumor and antiretroviral effect in certain individuals with KS and AIDS (88). Significant in vitro synergistic antiviral activity of IFN-a against HIV has also been described when combined with other antiretroviral agents (89).…”

Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma

“…2,6 KS is not curable, and while some cases of acquired immunodeficiency syndrome (AIDS)-related KS respond to highly active antiretroviral therapy (HAART) or interferon alpha, long-term palliative cytotoxic therapy is often required. [7][8][9][10][11] However, cumulative toxicity can limit the ability to continue otherwise effective therapy. The development of less toxic patient self-administered long-term therapy would thus be an important therapeutic advance.…”

Treatment of AIDS-Related Kaposi’s Sarcoma with Recombinant γ-Interferon

“…While treatment with ar-IFN has been shown sometimes to result in complete or partial response in AIDS-related KS [5][6][7][8] no data have been published on this effect of y-IFN. The rationale for using recombinant y-IFN was based on its immu nomodulatory effects [10] and its antitumor activity.…”

“…It is characterized by oppor tunistic infections and/or cancer, mainly Kaposi's sarcoma (KS), associated with immune abnormalities. Several immu nologic defects have been described, like anergy to delayed hypersensitivity recall skin test antigens, hyporesponsiveness of their lymphocytes to mitogenic stimulation, deficiency of Thelper cells, and impaired production of interleukin-2 and yinterferon in vitro [2], The development of KS has been observed in about one third of patients with AIDS [3], Although chemotherapy has been effective in the treatment of the tumor, relapse is usual [4], Recently several reports demonstrated an antitumor activity of recombinant a-interferon (a-IFN) in patients with AIDSrelated KS, the response rates ranging between 13% and 42% [5][6][7][8], however, no data have yet been reported for -y-interferon (-y-IFN). Since -y-IFN has also been shown to induce remissions in a variety of malignant tumors we investigated the antitumor activity of human recombinant -y-IFN in 4 patients with AIDSrelated KS.…”