Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma

J Clin Oncol. 2007 May 20;25(15):1974-8. doi: 10.1200/JCO.2006.05.9873.


Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Isotretinoin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplasms, Second Primary / prevention & control*
  • Prognosis
  • Prospective Studies
  • Recombinant Proteins
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Rate


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Isotretinoin