title: A phase II open-label study of recombinant human interleukin-12 in patients with stage IA, IB, or IIA mycosis fungoides.
abstract: BACKGROUND
  Interleukin-12 (IL-12) increases Th(1) cytokines, natural killer (NK) cells, and cytotoxic T-cell activities. Progression of mycosis fungoides is associated with Th(2) cytokines produced by a clonal proliferation of epidermotropic T-helper cells.
  
  
  OBJECTIVE
  To determine the safety and efficacy of subcutaneous recombinant human IL-12 (rhIL-12) in early mycosis fungoides (MF; stage IA-IIA) in a multi-center, open label clinical trial.
  
  
  METHODS
  rhIL-12 was administered biweekly (100 ng/kg for 2 weeks; 300 ng/kg thereafter). A modified severity-weighted assessment tool (SWAT) and the longest diameter of 5 index lesions measured efficacy.
  
  
  RESULTS
  Twenty-three MF patients (stage IA, 12 patients; IB, 9; and IIA, 2) had previously received >3 therapies. Ten of 23 patients (43%) achieved partial responses (PR); 7 (30%) achieved minor responses; and 5 (22%) had stable disease. The duration of PRs ranged from 3 to more than 45 weeks. Twelve (52%) ultimately progressed with mean time to progressive disease of 57 days (range, 28-805). Ten completed 6 months of therapy; 1 completed 24 months. Of patients not completing 6 months of therapy, 6 progressed and 6 others discontinued because of adverse events or withdrew consent. Seventeen patients had treatment-related adverse events that were generally mild or moderate in severity, including asthenia, headache, chills, fever, injection site reaction, pain, myalgia, arthralgia, elevated aspartate and alanine aminotransferase levels, anorexia, and sweating. One patient in PR died of hemolytic anemia, possibly exacerbated by rhIL-12 treatment.
  
  
  CONCLUSIONS
  The original company was purchased during the conduct of the trial and rhIL-12 is currently unavailable. The quality of life data were not available for inclusion.
  
  
  CONCLUSIONS
  Twice-weekly subcutaneously administered rhIL-12 (100 ng/kg escalated to 300 ng/kg) showed antitumor activity with a response rate of 43% in refractory patients. It was relatively well-tolerated in early-stage MF.
authors.affiliation: Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA. mduvic@mdanderson.org
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wood
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Elise
authors.initials: E
authors.lastname: Olsen
authors.forename: Francine
authors.initials: F
authors.lastname: Foss
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Laliberté
authors.forename: John L
authors.initials: JL
authors.lastname: Ryan
authors.forename: Kristilyn
authors.initials: K
authors.lastname: Zonno
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000473:pathology*; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D018664:Interleukin-12