Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck

TLDR

Patients who are disease‑free after local therapy for head‑and‑neck squamous‑cell carcinoma remain at high risk for recurrence and second primary tumors, and retinoids have shown efficacy in treating premalignant oral lesions and preventing epithelial carcinogenesis. The study prospectively evaluated whether daily high‑dose isotretinoin could prevent second primary tumors in 103 disease‑free patients with laryngeal, pharyngeal, or oral cavity squamous‑cell carcinoma. Patients were randomized to receive 50–100 mg/m²/day of isotretinoin or placebo for 12 months following surgery or radiotherapy. Isotretinoin did not affect recurrence rates but significantly lowered second primary tumors (4 % vs 24 %, P = 0.005), with most second cancers occurring in the head and neck, esophagus, or lung, and no second primaries in the treatment group.

Abstract

Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis.We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity. After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months.There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers. However, the isotretinoin group had significantly fewer second primary tumors. After a median follow-up of 32 months, only 2 patients (4 percent) in the isotretinoin group had second primary tumors, as compared with 12 (24 percent) in the placebo group (P = 0.005). Multiple second primary tumors occurred in four patients, all of whom were in the placebo group. Of the 14 second cancers, 13 (93 percent) occurred in the head and neck, esophagus, or lung.Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor.