Recombinant interferon alpha in the treatment of acquired immune deficiency syndrome-related Kaposi's sarcoma

Abstract

Acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) is more virulent than previously reported cases of KS and affects a much younger population. The cell of origin is lymphatic endothelium, with the histopathology characterized by a proliferation of small vessels with abnormal endothelial cells, extravasated erythrocytes, and spindle-shaped-cell infiltration. Clinical manifestations are pigmented, nodular lesions affecting the skin, mucous membranes, lymph nodes, and/or visceral organs. The head and oral cavity, uncommon sites in other KS populations, are frequently involved. Pain is not an early part of the clinical picture. AIDS-related KS is often widespread and rapidly progressive. However, the cause of death in most cases is attributed to opportunistic infection, which is believed to increase as a result of conventional cytotoxic chemotherapy. Recombinant interferon alpha has been the most thoroughly tested of immune-stimulating or nonimmunosuppressive drugs for the treatment of AIDS-related KS. An objective antineoplastic response rate (25% to 60%) comparable to single-agent chemotherapy with vinblastine or VP-16 has been demonstrated in several trials. Response rates to interferon alpha may be enhanced by such factors as absence of lymphoma-like B symptoms, low levels of circulating acid-labile interferon alpha, and absent history of recent serious infection. Varied drug dose, schedule, and route of administration have been employed; doses equal to or greater than 30 million U/day administered intravenously or intramuscularly appear to give the best results. Daily dosing regimens may induce tolerance for subjective toxicities (eg, fever, asthenia, and anorexia), which are often dose limiting. Direct immune stimulation following treatment with interferon alpha has not been conclusively established, but evidence suggests that respondents have low rates of opportunistic infection. Other recent studies demonstrate interferon alpha inhibiting activity against the AIDS-associated retrovirus in vitro and trials in vivo are in progress to define the clinical relevance of this observation.