PHASE-II TRIAL WITH DOSE TITRATION OF PACLITAXEL FOR THE THERAPY OF HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED KAPOSIS-SARCOMA

Purpose: To investigate the antitumor activity and safety of paclitaxe l in patients with advanced human immunodeficiency virus (HIV)-associa ted Kaposi's sarcoma (KS). Patients and Methods: Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overa ll quite immunosuppressed (median CD4 count, 15 cells/mu L). Paclitaxe l was initially administered at 135 mg/m(2) over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to ct maximum of 175 mg/m(2). Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. Results: Of 28 assessable patients, 20 had major responses ( 18 partial responses [PRs], one clinical complete response [CR], and o ne CR), for a major response rate of 71.4% (95% confidence interval [C I], 51.3% to 86.8%). Each of the five patients with pulmonary KS respo nded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxiciti es included late fevers, late rash, and eosinophilia. Two patients dev eloped an elevated creatinine concentration and one cardiomyopathy. Co nclusion: Paclitaxel has substantial activity against advanced HIV-ass ociated KS as a single agent, even in patients with pulmonary involvem ent or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vi s the other available therapies for this disease. This is a US governm ent work, There are no restrictions on its use.