Prospective randomized trial of two dose levels of interferon alfa with zidovudine for the treatment of Kaposi's sarcoma associated with human immunodeficiency virus infection: a Canadian HIV Clinical Trials Network study.
OBJECTIVE
Interferon alfa alone has shown antitumor activity against Kaposi's sarcoma (KS), and phase I and II clinical trials showed that interferon and zidovudine could be administered safely to patients with human immunodeficiency virus (HIV)-associated KS. These observations led to our trial of zidovudine with two dose levels of interferon alfa.


METHODS
HIV-positive patients with KS were eligible if they were older 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 daily and were randomized to receive-interferon alfa 1 million U or 8 million U subcutaneously daily.


RESULTS
The 108 eligible and assessable patients were well balanced for known prognostic factors. Response was reported in 31% of high-dose therapy and 8% of low-dose therapy patients (P=.011). Response at both dose levels was higher for patients with CD4 counts greater than 150 x 10(9)/L. The median time to progression was longer for patients in the 8-million U arm (18 v 13 weeks; P=.002). Both hematologic and nonhematologic toxicities were higher in the 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 patients who received 1 million U (P=.0002). No significant differences were reported with respect to improvement in CD4 count, elimination of p24 antigen, or development of opportunistic infections.


CONCLUSIONS
Zidovudine and moderate-dose-interferon alfa may be combined safely for the treatment of HIV-associated KS, and both response to treatment and toxicity are dose related.
Shepherd
F A
FA
Department of Medicine of the Toronto Hospital, Canada. fshepherd@torhosp.toronto.on.ca
Beaulieu
R
R
Gelmon
K
K
Thuot
C A
CA
Sawka
C
C
Read
S
S
Singer
J
J
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011446:Prospective Studies; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy*; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D016898:Interferon-alpha; D015215:Zidovudine