title: Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study.
abstract: We wished to evaluate the efficacy and safety of a low and an intermediate daily dose of interferon-alpha2b (IFN-alpha2b) with didanosine in patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). HIV-seropositive subjects with biopsy-confirmed cutaneous KS were randomized to receive either a low (1 million IU) or an intermediate (10 million IU) dose of IFN-alpha2b once daily with twice daily doses of didanosine. Treatment assignment was stratified by CD4 count. Response, toxicity, changes in CD4 counts, and survival were evaluated. Sixty-eight eligible subjects were accrued, 35 to low-dose and 33 to intermediate-dose IFN-alpha2b. The response rate was 40% in the low-dose group (95% CI, 24-58) and 55% in the intermediate-dose group (95% CI, 36-72) (p = 0.338). The median response duration was approximately 110 weeks in both groups. Intermediate-dose IFN induced grade 3/4 neutropenia more often (21% vs. 3%, p = 0.048) and grade 3/4 toxicity faster (p = 0.0231) and necessitated treatment discontinuation earlier for drug-related toxicities (p = 0.0416) than low-dose IFN. There were no significant differences in survival between the treatment groups. Baseline CD4 count was the only significant factor predicting response. Once-daily low-dose and intermediate-dose IFN-alpha2b induced similar response rates, which were achieved without optimal antiretroviral therapy. The slightly higher response rate in the intermediate-dose group was offset by its significantly poorer tolerance. These findings justify the use of lower, well-tolerated IFN doses for treatment of KS with currently used antiretroviral regimens.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. krowns@mskcc.org
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Von Roenn
authors.forename: Josephine
authors.initials: J
authors.lastname: Paredes
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Testa
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006679:HIV Seropositivity; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012514:Sarcoma, Kaposi / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D016898:Interferon-alpha; D016049:Didanosine