title: Interferon-alpha, zidovudine, and granulocyte-macrophage colony-stimulating factor: a phase I AIDS Clinical Trials Group study in patients with Kaposi's sarcoma associated with AIDS.
abstract: OBJECTIVE
  To increase the hematologic tolerance of interferon-alpha (IFN alpha) and zidovudine combination therapy by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF), and to evaluate the safety, tolerance, and potential efficacy of the combination in patients with Kaposi's sarcoma and AIDS.
  
  
  METHODS
  Seventeen patients with Kaposi's sarcoma associated with AIDS received zidovudine 200 mg orally every 4 hours and GM-CSF 5 micrograms/kg/d subcutaneously. Successive cohorts received IFN-alpha 2b at a daily subcutaneous dose of 5, 10, or 20 million units. The dose of GM-CSF was titrated to maintain the neutrophil count between 1 and 5 x 10(9) cells/L. Doses of all three drugs were reduced, as required, for nonhematologic toxicities.
  
  
  RESULTS
  GM-CSF induced leukocytosis in all patients. On average, a dose of 1.25 micrograms/kg/d was sufficient to maintain the neutrophil count within the desired range. The combination of 20 million units of IFN-alpha with zidovudine and GM-CSF induced dose-limiting toxicity in four of six patients. The major side effects were constitutional symptoms, which included malaise, anorexia, fatigue, fever, and were dose-limiting in three patients. Severe anemia and/or thrombocytopenia developed in three patients. Seven patients (41%; 95% confidence interval [CI], 18% to 64%) showed objective tumor regression that persisted for a median of 51 weeks. A rapid decrease in free-serum p24 antigen levels was observed in seven patients who had measurable levels at baseline; the mean time required to isolate human immunodeficiency virus (HIV-1) from peripheral-blood cells was increased by 7 days. The number and percentage of CD4-positive lymphocytes showed no significant change.
  
  
  CONCLUSIONS
  GM-CSF prevents neutropenia induced by the IFN-alpha and zidovudine combination and induced no adverse effects on immune function or HIV activity. However, nonhematologic toxicity precluded a major increase in the maximum-tolerated doses of IFN-alpha and zidovudine.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: S E
authors.initials: SE
authors.lastname: Krown
authors.forename: J
authors.initials: J
authors.lastname: Paredes
authors.forename: D
authors.initials: D
authors.lastname: Bundow
authors.forename: B
authors.initials: B
authors.lastname: Polsky
authors.forename: J W
authors.initials: JW
authors.lastname: Gold
authors.forename: N
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology / Q000517:prevention & control*; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D016898:Interferon-alpha; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor