A phase I study of recombinant human interferon-α(2a) or human lymphoblastoid interferon-α(n1) and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma

Margaret A Fischl, R. B. Uttamchandani, L. Resnick, R. Agarwal, M. A. Fletcher, J. Patrone-Reese, L. Dearmas, J. Chidekel, M. McCann, M. Myers

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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
Pages (from-to)1-10
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume4
Issue number1
StatePublished - Jan 16 1991

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Zidovudine
Interferon-alpha
Interferons
Neutropenia
Maximum Tolerated Dose
HIV-1
Anemia
Survival
Kaposi's Sarcoma
Lymphocyte Count
Virus Diseases
CD4 Lymphocyte Count
AIDS-related Kaposi sarcoma
Maintenance
Lymphocytes
Biopsy
Safety
Antigens
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Virology

Cite this

A phase I study of recombinant human interferon-α(2a) or human lymphoblastoid interferon-α(n1) and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. / Fischl, Margaret A; Uttamchandani, R. B.; Resnick, L.; Agarwal, R.; Fletcher, M. A.; Patrone-Reese, J.; Dearmas, L.; Chidekel, J.; McCann, M.; Myers, M.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 4, No. 1, 16.01.1991, p. 1-10.

Research output: Contribution to journalArticle

Fischl, MA, Uttamchandani, RB, Resnick, L, Agarwal, R, Fletcher, MA, Patrone-Reese, J, Dearmas, L, Chidekel, J, McCann, M & Myers, M 1991, 'A phase I study of recombinant human interferon-α(2a) or human lymphoblastoid interferon-α(n1) and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma', Journal of Acquired Immune Deficiency Syndromes, vol. 4, no. 1, pp. 1-10.
Fischl, Margaret A ; Uttamchandani, R. B. ; Resnick, L. ; Agarwal, R. ; Fletcher, M. A. ; Patrone-Reese, J. ; Dearmas, L. ; Chidekel, J. ; McCann, M. ; Myers, M. / A phase I study of recombinant human interferon-α(2a) or human lymphoblastoid interferon-α(n1) and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. In: Journal of Acquired Immune Deficiency Syndromes. 1991 ; Vol. 4, No. 1. pp. 1-10.
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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.",
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