PROSPECTIVE RANDOMIZED TRIAL OF 2 DOSE LEVELS OF INTERFERON-ALPHA WITH ZIDOVUDINE FOR THE TREATMENT OF KAPOSIS-SARCOMA ASSOCIATED WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - A CANADIAN HIV CLINICAL-TRIALS NETWORK STUDY

Purpose: Interferon alfa alone has shown antitumor activity against Ka posi's sarcoma (KS), and phase I and II clinical trials showed that in terferon and zidovudine could be administered safely to patients with human immunodeficiency virus (HIV)-associated KS. These observations l ed to our trial of zidovudine with two dose levels of interferon alfa. Methods: HIV-positive patients with KS were eligible if they were old er than 18 years of age, had a performance status of 0 to 2, and were free of active infection. All patients received zidovudine 500 mg dail y and were randomized to receive-interferon alfa 1 million U or 8 mill ion U subcutaneously daily. Results: The 108 eligible and assessable p atients were well balanced for known prognostic factors. Response was reported in 31% of high-dose therapy and 8% of low-dose therapy patien ts (P = .011). Response at both dose levels was higher for patients wi th CD4 counts greater than 150 x 10(9)/L. The median time to progressi on was longer for patients in the 8-million U arm (l8 v 13 weeks; P = .002). Both hematologic and nonhematologic toxicities were higher in t he high-dose arm; 50 of 54 patients who received 8 million U required dose alterations in the first 4 months compared with only 19 of 53 pat ients who received 1 million U (P = .0002). No significant differences were reported with respect to improvement in CD4 count, elimination o f p24 antigen, or development of opportunistic infections. Conclusion: Zidovudine and moderate-dose-interferon alfa may be combined safely f or the treatment of HIV-associated KS, and both response to treatment and toxicity are dose related. (C) 1998 by American Society of Clinica l Oncology.