title: Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up.
abstract: OBJECTIVE
  To evaluate the long-term effects of the combination of isotretinoin, interferon alfa-2a, and vitamin E in locally advanced squamous cell carcinoma of the head and neck.
  
  
  METHODS
  Phase 2 prospective study.
  
  
  METHODS
  Tertiary care academic medical centers.
  
  
  METHODS
  Forty-five patients entered this study. All patients had stage III or IV squamous cell carcinoma of the head and neck and had been treated with surgical resection, radiation, or both. All patients were then treated with bioadjuvant chemopreventive treatment for 12 months. We previously reported a 24-month median follow-up of this phase 2 trial of the combination of isotretinoin, interferon alfa-2a, and vitamin E as bioadjuvant therapy after definitive local therapy. In that study, all 45 patients completed treatment, but 1 patient was excluded from analysis of recurrence and development of second primary tumors. Main Outcome Measure Longer-term (49.4-month median) follow-up.
  
  
  RESULTS
  Among the 45 patients treated under the protocol, only 7 patients (16%) had died. Nine (20%) of 45 patients experienced progressive disease. Only 1 second primary tumor (acute promyelocytic leukemia) occurred during follow-up, and no aerodigestive second primary tumors occurred among the 45 patients. The 5-year progression-free survival and overall survival percentages were 80% (95% confidence interval, 65.1%-89.1%) and 81.3% (95% confidence interval, 63.7%-90.9%), respectively. These results are significantly better than the historical 5-year overall survival for advanced squamous cell carcinoma of the head and neck (approximately 40%).
  
  
  CONCLUSIONS
  The bioadjuvant combination is highly effective in preventing recurrence and second primary tumors, and its role as standard therapy in advanced squamous cell carcinoma of the head and neck is being investigated in a randomized phase 3 study.
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Seixas-Silva
authors.forename: Thomas
authors.initials: T
authors.lastname: Richards
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: H Samuel
authors.initials: HS
authors.lastname: Wieand
authors.forename: Ed
authors.initials: E
authors.lastname: Kim
authors.forename: Barbara
authors.initials: B
authors.lastname: Murphy
authors.forename: Marites
authors.initials: M
authors.lastname: Francisco
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D004359:Drug Therapy, Combination; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D015474:Isotretinoin / Q000008:administration & dosage*; D016609:Neoplasms, Second Primary; D011446:Prospective Studies; D011994:Recombinant Proteins; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014810:Vitamin E; D015474:Isotretinoin