title: Antitumor activity of oral 9-cis-retinoic acid in HIV-associated Kaposi's sarcoma.
abstract: OBJECTIVE
  To assess the efficacy, safety and tolerance of oral 9-cis-retinoic acid in HIV-infected patients with Kaposi's sarcoma.
  
  
  METHODS
  Sixty-six patients with AIDS-related Kaposi's sarcoma were enrolled at 14 centers; 60 received the study medication and were analyzed and, of these, 45 (75%) had received prior therapy for Kaposi's sarcoma. Once daily oral 9-cis-retinoic acid (alitretinoin, Panretin) was administered at doses up to 140 mg/m2. Most patients (72%) received a maximum dose of 100 mg/m2. Response was assessed using AIDS Clinical Trials Group (ACTG) criteria.
  
  
  RESULTS
  The median age was 38 years and the median absolute CD4 cell count was 194 x 10(6) cells/l (range 6-784 x 10(6)). Despite the use of three- and four-drug antiviral regimens (83%), the median HIV RNA at baseline was 8701 copies/ml [range < 500 (lower limit of detection) to 4.24 x 10(6)]. The tumor response rate was 37% (95% confidence interval 25-49). Tumor response was associated with improved quality-of-life measures. There was a significant increase in interleukin 6 (IL-6) levels from baseline to week 4. Responders had significantly lower baseline soluble IL-6 receptor levels (P = 0.029) than non-responders. The median time to response was 9 weeks (mean, 13 weeks; range, 4-36). HIV RNA levels did not change significantly during therapy nor did they correlate with tumor responses. Study drug was discontinued by 28 patients for adverse events, which included headache (13) and skin toxicity (10).
  
  
  CONCLUSIONS
  Oral 9-cis-retinoic acid is an active antitumor drug for AIDS-related Kaposi's sarcoma. Treatment is associated with skin and constitutional toxicity and further studies are needed to improve its long-term tolerance.
authors.affiliation: AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, 2001 Third Avenue South, Room 1078, Birmingham, AL 35223, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Miles
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Dezube
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Fletcher
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Saville
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kaplan
authors.forename: Jerome
authors.initials: J
authors.lastname: Groopman
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Timothy
authors.initials: T
authors.lastname: Cooley
authors.forename: Jamie
authors.initials: J
authors.lastname: Von Roenn
authors.forename: Alvin
authors.initials: A
authors.lastname: Friedman-Kien
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004361:Drug Tolerance; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood; D012449:Safety; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D012367:RNA, Viral; D019947:Receptors, Interleukin-6; D000077556:Alitretinoin; D014212:Tretinoin