Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma

Steven A. Miles, Bruce J. Dezube, Jeannette Y. Lee, Susan E. Krown, Mary Ann Fletcher, M. Wayne Saville, Lawrence Kaplan, Jerome Groopman, David T. Scadden, Timothy Cooley, Jamie Von Roenn, Alvin Friedman-Kien

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Abstract

Objective: To assess the efficacy, safety and tolerance of oral 9-cis-retinoic acid in HIV-infected patients with Kaposi's sarcoma. Methods: Sixty-six patients with AIDS-related Kaposi's sarcoma were enrolled at 14 centers; 60 received the study medication and were analyzed and, of these, 45 (75%) had received prior therapy for Kaposi's sarcoma. Once daily oral 9-cis-retinoic acid (alitretinoin, Panretin) was administered at doses up to 140 mg/m2. Most patients (72%) received a maximum dose of 100 mg/m2. Response was assessed using AIDS Clinical Trials Group (ACTG) criteria. Results: The median age was 38 years and the median absolute CD4 cell count was 194 × 106 cells/l (range 6-784 × 106). Despite the use of three- and four-drug antiviral regimens (83%), the median HIV RNA at baseline was 8701 copies/ml [range < 500 (lower limit of detection) to 4.24 × 106]. The tumor response rate was 37% (95% confidence interval 25-49). Tumor response was associated with improved quality-of-life measures. There was a significant increase in interleukin 6 (IL-6) levels from baseline to week 4. Responders had significantly lower baseline soluble IL-6 receptor levels (P = 0.029) than non-responders. The median time to response was 9 weeks (mean, 13 weeks; range, 4-36). HIV RNA levels did not change significantly during therapy nor did they correlate with tumor responses. Study drug was discontinued by 28 patients for adverse events, which included headache (13) and skin toxicity (10). Conclusion: Oral 9-cis-retinoic acid is an active antitumor drug for AIDS-related Kaposi's sarcoma. Treatment is associated with skin and constitutional toxicity and further studies are needed to improve its long-term tolerance.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalAIDS
Volume16
Issue number3
DOIs
StatePublished - Feb 15 2002

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Keywords

  • 9-cis-retinoic acid
  • Antitumor therapy
  • HIV-1
  • Kaposi's sarcoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miles, S. A., Dezube, B. J., Lee, J. Y., Krown, S. E., Fletcher, M. A., Saville, M. W., Kaplan, L., Groopman, J., Scadden, D. T., Cooley, T., Von Roenn, J., & Friedman-Kien, A. (2002). Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma. AIDS, 16(3), 421-429. https://doi.org/10.1097/00002030-200202150-00014