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; H. Clifford Lane, MD
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.
Joseph A. Kovacs, Lawrence Deyton, Richard Davey, Judith Falloon, Kathryn Zunich, Dianne Lee, et al. Combined Zidovudine and Interferon-α Therapy in Patients with Kaposi Sarcoma and the Acquired Immunodeficiency Syndrome (AIDS). Ann Intern Med. 1989;111:280–287. doi: 10.7326/0003-4819-111-4-280
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Published: Ann Intern Med. 1989;111(4):280-287.
Hematology/Oncology, Infectious Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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