Prevention of second primary tumours with etretinate in squamous cell carcinoma of the oral cavity and oropharynx. Results of a multicentric double-blind randomised study

Abstract

Patients who are cured from head and neck carcinomas remain at high risk for developing a second primary in the head and neck area. It is now clear that retinoids exert a prophylactic action on the development of epithelial cancers when tested on laboratory animals and on human premalignant lesions. They are now used in the chemoprevention of epithelial cancers in randomised trials evaluating their efficacy. We prospectively studied 316 patients who developed squamous cell carcinoma of the head and neck, classified as T1 T2 , N0 N1 ≤ 3 cm , M0 according to the UICC TNM classification. Patients were randomly assigned to receive orally, either etretinate (a loading dose of 50 mg/day for the first month, followed by a dose of 25 mg/day in the following months) or a placebo for 24 months. Adjuvant treatment began no later than 15 days after surgery and/or the initiation of radiotherapy. The 5-year survival rate and disease-free survival rate are similar in the two groups. There are no significant differences regarding either local, regional and distant relapses. After a median follow-up of 41 months (range 0–81), 28 patients in the etretinate group and 29 in the placebo group developed a second cancer with, respectively, 12 and 13 in the head and neck region. Adjuvant treatment was definitively discontinued mainly due to toxicity in 33% of patients in the etretinate group versus 23% in the placebo group ( P < 0.05). Etretinate, a second-generation retinoid, does not prevent second primary tumours in patients who have been treated for squamous cell carcinoma of the oral cavity and oropharynx.