title: Chemoprevention of head and neck cancer with retinoids: a negative result.
abstract: OBJECTIVE
  To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to enter appropriate patients into this trial.
  
  
  METHODS
  One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment.
  
  
  METHODS
  Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for 1 year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years.
  
  
  METHODS
  The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured.
  
  
  RESULTS
  There was no significant difference in the occurrence of second primary disease (P = .90), the recurrence of primary disease (P = .70), or disease-free time (P = .80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival.
  
  
  CONCLUSIONS
  With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Princess Alexandra Hospital, Woolloongabba, Australia. cpmedical@hotkey.net.au
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Perry
authors.forename: Maurice
authors.initials: M
authors.lastname: Stevens
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Rabie
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Yarker
authors.forename: Julie
authors.initials: J
authors.lastname: Cochrane
authors.forename: Emily
authors.initials: E
authors.lastname: Perry
authors.forename: Robert
authors.initials: R
authors.lastname: Traficante
authors.forename: William
authors.initials: W
authors.lastname: Coman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018890:Chemoprevention / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*; D009517:New South Wales; D016012:Poisson Distribution; D011336:Probability; D016016:Proportional Hazards Models; D012176:Retinoids / Q000627:therapeutic use*; D018570:Risk Assessment; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D012176:Retinoids