Taking a vitamin A derivative called isotretinoin did not reduce the risk of second primary tumors or improve survival in patients with stage I or II head and neck squamous cell cancers (HNSCC), according to a study in the Journal of the National Cancer Institute. In addition, current smokers had an increased risk of second primary cancers and death.
HNSCCs are the fifth most common cancers and sixth leading cause of cancer related death today. In 2002, there were 600,000 new cases diagnosed worldwide. Some studies have suggested that vitamin A derivatives called retinoids may halt or even reverse growth of head and neck tumors. A clinical trial of high doses of a retinoid called isotretinoin, widely used to treat cystic acne, in patients with HNSCC found that those receiving isotretinoin developed fewer second primary tumors, particularly smoking-related tumors. However, there were substantial side effects among those who received the high-dose isotretinoin, and subsequent studies of the compound have shown mixed results.
To assess the effect of lower, more tolerable doses of isotretinoin on the development of second primary tumors and survival among patients with early-stage HNSCC, Fadlo R. Khuri, M.D., of the Emory University School of Medicine in Atlanta, and colleagues conducted a randomized clinical trial of 1190 patients diagnosed with stage I or II HNSCC. Patients were randomly assigned to receive low-dose isotretinoin (30 mg/day) or a placebo for 3 years. They continued to monitor the patients for 4 or more years after treatment. This clinical trial is the largest chemoprevention study to date to examine the use of retinoids in patients with early-stage HNSCC.
The study found that low-dose isotretinoin did not reduce the rate of second primary tumors or improve overall survival compared with a placebo. Current smokers in both the treatment and placebo groups had an increased rate of second primary tumors and death. The authors conclude that the study provides substantial evidence that doctors should work with patients on smoking cessation, and they do not recommend isotretinoin monotherapy as a preventive agent for second primary tumors in people with stage I or II HNSCC.