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.
From the AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, Alabama, USA. *See the Appendix for members of the AIDS Malignancy Consortium.
Requests for reprints to: Dr J. Y. Lee, 2001 Third Avenue South – Room 1078, Birmingham, Alabama 35223, USA.
Received: 8 June 2001;
revised: 21 September 2001; accepted: 2 October 2001.
Sponsorship: this work was funded in part by support from Ligand Pharmaceuticals Inc. and the National Cancer Institute (Grant nos. U01 CA70079, U01 CA70081, U01 CA70068, U01 CA70075, U01 CA70047, U01 CA70054, U01 CA70080, U01 CA71375, U01 CA70062, and U01 CA70019).