AIDS-associated Kaposi's sarcoma: Is there still a role for interferon alfa?

Abstract

Interferon alfa (IFNA) was one of the first agents to be used therapeutically in AIDS-associated Kaposi's sarcoma (KS) more than 25 years ago, and induces tumor regression in a subset of patients. Although much has been learned about the clinical role of IFNα in KS treatment, little is currently known about the mechanism(s) by which IFNA causes KS regression. This is despite a growing understanding of both KS pathogenesis and relevant IFNA activities. To a large extent other agents have supplanted IFNA as treatments for KS, but there may still remain a therapeutic role for IFNA, possibly in combination with other agents targeting angiogenesis and/or HHV-8-encoded human gene homologs that encode proteins involved in cell cycle regulation and signaling. KeywordsInterferon; Kaposi's sarcoma In 1995, when I was honored as a recipient of the ISICR Milstein Award, the AIDS epidemic had recently begun its 15 th year and the human immunodeficiency virus (HIV-1) had been isolated some 12 years previously [1]. However, the virus associated with Kaposi's sarcoma (KS), the most common AIDS-associated malignancy, had been described less than a year earlier [2], its significance was still in some question and its role in KS development had not been characterized, and the active combination drug regimens with which we now treat HIV infection had not yet become widely available. Recombinant interferon alfa preparations (IFNα2a and IFNα2b), which had received approval from the U.S. Food and Drug Administration (FDA) for treatment of AIDS-associated KS in 1988, were still the only approved drugs for systemic treatment of KS (the chemotherapeutic agent, liposomal doxorubicin, would receive FDA approval later in 1995, as did liposomal daunorubicin in 1996 and paclitaxel in 1997). Now, more than a quarter century after the first published reports describing AIDS and its association with KS [3-6] and our first modestly successful attempts to treat KS with IFNα [7], this agent is used infrequently to treat KS, although it still finds use in HIV-infected individuals co-infected with hepatitis C. In this brief review, I will summarize some of the history of IFNα in the treatment of AIDS-associated KS, concentrating on examples of clinical trials in which I have personally been involved, and consider whether there remains a potentially valuable role for this agent in KS treatment.

AIDS-Related Kaposi's Sarcoma Can Occur during Peginterferon-α and Ribavirin Therapy for Chronic Hepatitis C Infection

“…4,5 The lack of HAART combined with a rapid decrease in absolute CD4 counts (despite a persistent satisfactory percentage), due to PegIFN treatment, was responsible for the development of KS in this HHV8-seropositive patient. Despite its potential activity on KS, PegIFN was unable to prevent the occurrence of KS and HHV8 replication.…”

Trends in Kaposi’s Sarcoma in Miami Beach from 1987 to 2007

“…Although paclitaxel has been thought to be potentially more toxic than liposomal doxorubicin, it has been established as a second-line treatment for KS [64–71]. Recombinant interferon alpha is another agent approved for the treatment of AIDS-related KS and has produced beneficial responses in 20–40 percent of patients [72, 73]. …”

Interferons

“…Kaposi sarcoma [7] Interferon-α2a is used for the treatment of AIDS-related Kaposi sarcoma with a CD4 count greater than …”