Treatment of AIDS-related cutaneous Kaposi's sarcoma with topical alitretinoin (9-cis-retinoic acid) gel

Background: Kaposi's sarcoma (KS) is the most frequent malignancy in patien ts with HIV. Given the promise that retinoids show in the treatment of vari ous hyperproliferative skin disorders and in vitro evidence of inhibition o f proliferation of KS cells, a randomized, controlled clinical trial was co nducted. Methods and Results: A 12-week, multicenter, randomized, double-blind, vehi cle-controlled safety and efficacy evaluation of topical alitretinoin 0.1% gel applied to cutaneous KS lesions was conducted in HIV-infected patients. The primary efficacy endpoint was the patient's response rate, as determin ed by evaluating six index lesions representative of the patient's overall KS cutaneous disease using AIDS Clinical Trials Group (ACTG) response crite ria applied to topical therapy. Of 268 patients entered in the blinded trea tment phase of the study (alitretinoin group, n = 134; vehicle group, n = 1 34), 47 patients (35%) treated with alitretinoin 0.1% gel had a positive re sponse, compared with 24 patients (18%) treated with vehicle gel. Of 184 pa tients receiving open-label alitretinoin treatment following the blinded ph ase of the trial, 90 patients (49%) met criteria for a positive response. T his superior efficacy of alitretinoin gel over vehicle gel was maintained w hen the data were adjusted or analyzed for age, race, Karnofsky scores, bas eline CD4(+) lymphocyte counts, number of raised lesions at baseline, and a ggregate area of index lesions. Alitretinoin 0.1% gel was superior to vehic le gel regardless of the number of concurrent antiretroviral therapies. Mos t adverse events were mild to moderate in severity, limited to the applicat ion site, and reversible on reduction in frequency or suspension of applica tion. Relatively few patients (7%) discontinued alitretinoin therapy becaus e of to related adverse events. Conclusions: The results show that alitretinoin gel application is safe and generally well tolerated, and they indicate the superiority of alitretinoi n 0.1% gel over vehicle gel in the treatment of cutaneous AIDS-related KS l esions.