Isotretinoin, Interferon Alfa, and Vitamin E in Treating Patients With Stage III or Stage IV Head and Neck Cancer
Condition: Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy such as isotretinoin use different ways to stop tumor
      cells from dividing so they stop growing or die. Interferon alfa may interfere with the
      growth of tumor cells. Vitamin E may be able to decrease side effects caused by isotretinoin.
      It is not yet known whether combining isotretinoin and interferon alfa with vitamin E is more
      effective than observation in preventing recurrence of head and neck cancer after surgery
      and/or radiation therapy.

      PURPOSE: Randomized phase III trial to compare the effectiveness of isotretinoin and
      interferon alfa combined with vitamin E with that of observation in treating patients who
      have undergone surgery and/or radiation therapy for stage III or stage IV head and neck
      cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the efficacy of adjuvant isotretinoin, interferon alfa, and vitamin E, in
           terms of incidence of primary disease recurrence and secondary primary tumor
           development, in patients with stage III or IV squamous cell carcinoma of the head and
           neck previously treated with definitive surgical excision and/or postoperative
           radiotherapy.

        -  Determine the qualitative and quantitative toxicity of this regimen in these patients.

        -  Compare the overall and disease-free survival of patients treated with this regimen vs
           those who undergo observation only.

        -  Determine whether alterations of p53 gene, retinoic acid receptors, retinoid-regulated
           gene, and interferon-responsive genes are associated with clinical outcome in these
           patients.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to T
      stage (T1 or T2 vs T3 or T4), N stage (N0 or N1 vs N2 or N3), prior therapy (complete tumor
      resection vs resection and radiotherapy/chemoradiotherapy vs radiotherapy or
      chemoradiotherapy alone), and prior chemotherapy (yes vs no). Patients are randomized to 1 of
      2 treatment arms.

        -  Arm I: Patients receive oral isotretinoin once daily, interferon alfa subcutaneously 3
           times weekly, and oral vitamin E 3 times daily. Treatment repeats every month for 12
           courses (1 year) in the absence of disease recurrence or unacceptable toxicity.

        -  Arm II: Patients undergo observation only for 1 year. Patients are followed every 3
           months for 2 years and then every 6 months for 3 years.

      PROJECTED ACCRUAL: A total of 376 patients (188 per treatment arm) will be accrued for this
      study within 3.75 years.
    

Intervention name(s): recombinant interferon alfa; vitamin E; isotretinoin; adjuvant therapy
Intervention type(s): Biological; Dietary Supplement; Drug; Procedure
Intervention MeSH terms: Vitamin E; Interferons; Interferon-alpha; Isotretinoin
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx