PHASE I II STUDY OF INTERMITTENT ALL-TRANS-RETINOIC ACID, ALONE AND IN COMBINATION WITH INTERFERON ALFA-2A, IN PATIENTS WITH EPIDEMIC KAPOSIS-SARCOMA/

purpose: A phase I/II study of oral all-trans-retinoic acid (ATRA; tre tinoin), administered every other week alone and then in combination w ith interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Patien ts and Methods: Thirteen patients with HIV-associated KS, eight of who m had more than 100 CD4 cells/mu L, were entered. The protocol initial ly called for patients to receive 150 mg/m(2)/d of ATRA every other we ek. However, this regimen wets associated with headaches, and the init ial dose of ATRA was reduced to 40 mg/m(2)/d orally in three divided d oses, increasing to a maximum of 100 mg/m(2)/d. After 12 weeks, IFN al fa-2a could be added. Results: The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 a ssessable patients, 10 had progressive disease and two had stable dise ase on ATRA alone. One of eight assessable patients who went on to rec eive ATRA plus IFN alfa-2a had a partial response (PR), There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count d uring treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebovfided when treatment was re sumed after a week without the drug. Conclusion: Intermittent ATRA the rapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy, However, w e were unable to document antitumor activity in patients with HIV-asso ciated KS.