title: Phase I/II study of intermittent all-trans-retinoic acid, alone and in combination with interferon alfa-2a, in patients with epidemic Kaposi's sarcoma.
abstract: OBJECTIVE
  A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with 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).
  
  
  METHODS
  Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added.
  
  
  RESULTS
  The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug.
  
  
  CONCLUSIONS
  Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.
authors.affiliation: Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bailey
authors.forename: J M
authors.initials: JM
authors.lastname: Pluda
authors.forename: A
authors.initials: A
authors.lastname: Foli
authors.forename: M W
authors.initials: MW
authors.lastname: Saville
authors.forename: S
authors.initials: S
authors.lastname: Bauza
authors.forename: P C
authors.initials: PC
authors.lastname: Adamson
authors.forename: R F
authors.initials: RF
authors.lastname: Murphy
authors.forename: R B
authors.initials: RB
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Broder
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000150:complications; D006261:Headache / Q000139:chemically induced; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012044:Regression Analysis; D012074:Remission Induction; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy / Q000821:virology; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin