Low-dose isotretinoin no help against second primary head and neck tumors

Last Updated: 2006-04-17 8:39:23 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - Low doses of isotretinoin do not reduce the risk of second primary tumors or increase survival in patients with head and neck cancer, researchers report in the April 5th issue of the Journal of the National Cancer Institute.

Dr. Fadlo R. Khuri of Emory University School of Medicine, Atlanta and colleagues note that preclinical and clinical studies have suggested that high doses of the agent are helpful in patients with head and neck squamous cell carcinoma. However, toxicity is substantial.

To investigate whether a low-dose approach might help avoid this problem and also be useful, the researchers randomized 1190 patients who had been treated for stage I or II disease to isotretinoin 30 mg per day or placebo for 3 years.

Patients were followed for more than 4 years. Current smokers had a higher risk of second tumors than never smokers (hazard ratio 1.64). This was also true of death from any cause (hazard ratio 2.61). Overall, some 31% of primary second tumors were in the lung and 17% in the oral cavity.

However, the team also found that the active treatment led to no significant decrease in the rate of second primary tumors or to any increase in survival.

Lead author of an accompanying editorial, Dr. Sarah J. Freemantle of Dartmouth Medical School, Hanover, New Hampshire, told Reuters Health that "this is a definitive phase III trial. Low-dose isotretinoin was not effective in preventing second primary tumors in head and neck cancer patients."

Nevertheless, she concluded, "the chemoprevention field has evolved and newer retinoids and combination regimens must still be explored."

J Natl Cancer Inst 2006;98:441-450,426-427.