Beta-Interferon Therapy in Patients with Poor-Prognosis Kaposi Sarcoma Related to the Acquired Immunodeficiency Syndrome (AIDS)

doi:10.1059/0003-4819-112-8-582

Beta-Interferon Therapy in Patients with Poor-Prognosis Kaposi Sarcoma Related to the Acquired Immunodeficiency Syndrome (AIDS)

A Phase II Trial with Preliminary Evidence of Antiviral Activity and Low Incidence of Opportunistic Infections

Abstract

Study Objective: To study the efficacy of high doses of beta-ser-interferon (recombinant human 17-serine beta-interferon) in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma.

Design: A nonrandomized, controlled trial of two high-dose regimens of beta-ser-interferon administered until tumor progression, toxicity, or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection occurred.

Setting: An AIDS treatment clinic at a tertiary care center.

Patients: A sequential sample of 39 patients with biopsy-proven, AIDS-related Kaposi sarcoma were enrolled during a 2-year period. Thirty-eight patients were evaluable for response. Most patients (35 of 38) had one or more of the following clinical or laboratory predictors for a poor response to interferon therapy: HIV p24 antigenemia, low CD4 cell numbers, elevated beta₂-microglobulin levels, previous opportunistic infections, or previous systemic chemotherapy.

Interventions: Beta-ser-interferon was self-administered subcutaneously at home 5 days per week. The first 21 patients used 90 million IU/d, and the remainder used 180 million IU/d.

Measurements and Main Results: Six patients (16%) had a major clinical response, and 15 (39%) had stable disease for prolonged periods. Toxicities were minimal; the major toxicity was a skin reaction at the injection site. The HIV p24 antigen level declined more than 50% in 8 of the 19 patients with initial values greater than 50 pg/mL. Antiretroviral activity and antitumor activity were seen only in patients with normal initial beta₂-microglobulin levels. Minimal changes were seen in CD4 and CD8 cell numbers. Only 1 patient had an opportunistic infection while on study, but five other patients developed infections after treatment was discontinued for an incidence of six opportunistic infections in 285 patient-observation months.

Conclusions: The high doses of interferon did not improve the major response rate in patients with poor-prognosis, AIDS-related Kaposi sarcoma. There was, however, a suggestion of antiviral activity in patients with normal beta₂-microglobulin levels and a decrease in the expected incidence of opportunistic infections.

Article and Author Information

From UCLA AIDS Center and UCLA School of Public Health, Los Angeles, California; Hospital Universitario, Rio de Janiero, Brazil; and Triton Biosciences, Inc., Alameda, California. For current author addresses, see end of text.
Grant Support: In part by grants from the State of California under the direction of the Universitywide Task Force on AIDS (87LA039 and 89C-CC86LA), National Institute of Allergy and Immunological Diseases (AI27660), American Cancer Society (SAM), and Triton Biosciences, Inc.
Requests for Reprints: Steven A. Miles, MD, Division of Hematology-Oncology, UCLA AIDS Center, Room 60-051, Center for Health Sciences, Los Angeles, CA 90024-1793.
Current Author Addresses: Dr. Miles, Ms. Carden, and Dr. Mitsuyasu: Division of Hematology-Oncology, UCLA AIDS Center, Room 60-051, Center for Health Sciences, Los Angeles, CA 90024-1793.

Dr. Wang: Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA 90024.

Dr. Cortes: Hospital Universitario-UFRJ, Departamento de Clinica Medica, Av. Brigadeiro Trompowsky S/N, Ilha do Fundao, Rio de Janiero, RJ. Brazil.

Dr. Marcus: Triton Biosciences, Inc., 1501 Harbor Bay Parkway, Alameda, CA 94501.