A phase i study of recombinant human interferon-α2a or human lymphoblastoid interferon-αn1 and concomitant zidovudine in patients with aids-related kaposi’s sarcoma

Margaret A. Fischl, Raj B. Uttamchandani, Lionel Resnick, Ram Agarwal, Mary Ann Fletcher, Janie Patrone-Reese, Lisa Dearmas, Jane Chidekel, Mary McCann, Maureen Myers

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-α and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-α was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-α (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-α and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p < 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p < 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p < 0.001) and a pretreatment CD4 cell count ≥200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-α and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume4
Issue number1
StatePublished - Jan 1991

Keywords

  • Human immunodeficiency virus type 1 (hiv)
  • Interferon-α-Zidovudine (azt)
  • Kaposi’s sarcoma (ks)

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Fischl, M. A., Uttamchandani, R. B., Resnick, L., Agarwal, R., Fletcher, M. A., Patrone-Reese, J., Dearmas, L., Chidekel, J., McCann, M., & Myers, M. (1991). A phase i study of recombinant human interferon-α2a or human lymphoblastoid interferon-αn1 and concomitant zidovudine in patients with aids-related kaposi’s sarcoma. Journal of Acquired Immune Deficiency Syndromes, 4(1), 1-10.