Combined Zidovudine and Interferon-α Therapy in Patients with Kaposi Sarcoma and the Acquired Immunodeficiency Syndrome (AIDS)
- Joseph A. Kovacs, MD;
- Lawrence Deyton, MD;
- Richard Davey, MD;
- Judith Falloon, MD;
- Kathryn Zunich, MD;
- Dianne Lee, MS;
- Julia A. Metcalf;
- Joseph W. Bigley, MS;
- Leigh A. Sawyer, DVM, MPH;
- Kathryn C. Zoon, PhD;
- Henry Masur, MD;
- Anthony S. Fauci, MD; and
- H. Clifford Lane, MD
Abstract
Study Objective: To evaluate the toxicity and potential clinical efficacy of combined therapy with zidovudine and interferon-α for patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS).
Design: Nonrandomized, open trial study.
Setting: Outpatient clinic of a government referral-based research hospital.
Patients: Volunteer sample of 39 patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma.
Interventions: Patients received zidovudine, 250, 100, or 50 mg orally every 4 hours; 6 weeks after interferon-α was begun at a dose of 5 million U/d, and the dose was increased every 2 weeks until a maximum tolerated dose was determined. Patients then received the maximum tolerated dose of the combination for a minimum of 12 weeks before formal efficacy evaluations.
Measurements and Main Results: In the dose-escalation phase, the ability to tolerate interferon-α was clearly related to the zidovudine dose. Of the 13 patients receiving 250 mg of zidovudine, only 1 patient was able to tolerate at least 10 million U/d of interferon-α. Of the 12 patients receiving 100 mg of zidovudine, 8 tolerated 10 million U/d, 5 tolerated 15 million U/d, and none tolerated higher doses. Of the 12 patients receiving 50 mg of zidovudine, 8 tolerated 10 million U/d, 7 tolerated 15 million U/d, and 6 tolerated 20 million U/d or more. Dose-limiting toxicities included neutropenia (57%), fatigue (16%), thrombocytopenia (14%), and hepatic dysfunction (10%). Of the 22 patients who received a stable dose of both drugs for 12 weeks, 11 patients had a complete or partial tumor response and 8 showed an anti-HIV effect. Peak serum levels of interferon-α (32 to 250 U/mL) and zidovudine (0.40 to 3.85 µM) were in the ranges previously shown to be synergistic against HIV.
Conclusions: Combination therapy with zidovudine and interferon-α can be administered to patients with HIV infection and Kaposi sarcoma in doses that effect antiviral and antitumor responses; it appears to have a potential role in managing such patients.
Article and Author Information
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From the National Institute of Allergy and Infectious Diseases and Clinical Center, National Institutes of Health, Bethesda, Maryland; Burroughs Wellcome Company, Research Triangle Park, North Carolina; and Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland. For current author addresses, see end of text.
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Requests for Reprints: H. Clifford Lane, MD, Laboratory of Immunoregulation, NIAID, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 11B-13, Bethesda, MD 20892.
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Current Author Addresses: Drs. Kovacs and Masur: Clinical Center, Building 10, Room 10D48, National Institutes of Health, Bethesda, MD 20892.
Drs. Davey, Falloon, Zunich, Lee, Lane, and Ms. Metcalf: NIAID, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 1IB-13, Bethesda, MD 20892.
Dr. Deyton: AIDS Program, NIAID, National Institutes of Health, 6003 Executive Boulevard, Room 247P, Rockville, MD 20852. Mr. Bigley: Burroughs Wellcome Company, 3030 Cornwallis Road, Research Triangle Park, NC 27709.
Dr. Sawyer: FDA, CBER, DV Laboratory of Retrovirology Research, 8800 Rockville Pike, HFB-580, Bethesda, MD 20892. Dr. Zoon: Building 29A, Room 2A17/2D24, CBER, 8800 Rockville Pike, Bethesda, MD 20892.
Dr. Fauci: NIAID, National Institutes of Health, Building 31, Room 7A03, Bethesda, MD 20892.
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