title: Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma.
abstract: OBJECTIVE
  To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC.
  
  
  METHODS
  Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation.
  
  
  RESULTS
  At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities.
  
  
  CONCLUSIONS
  Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230-1439, USA.
authors.forename: Abenaa M
authors.initials: AM
authors.lastname: Brewster
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
authors.forename: John L
authors.initials: JL
authors.lastname: Clifford
authors.forename: Mary Jo T Necesito
authors.initials: MJ
authors.lastname: Reyes
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
authors.forename: Anita L
authors.initials: AL
authors.lastname: Sabichi
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Robert
authors.initials: R
authors.lastname: Collins
authors.forename: Christina A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D015474:Isotretinoin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016609:Neoplasms, Second Primary / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin