Safety of high-dose vitamin A. Randomized trial on lung cancer chemoprevention.

The paper reports on the efficacy and side effects of high-dose vitamin A, administered as adjuvant treatment for resected stage I lung cancer in a randomized clinical trial. After a median follow-up of 28 months, 283 patients were evaluable: 138 allocated to treatment with retinol palmitate (300,000 IU daily for at least 12 months) and 145 to standard observation. The clinical results available to date do well justify a continuation of the study. Skin dryness and desquamation were the most frequent symptoms, affecting 60% of all treated patients. Other symptoms such as dyspepsia, headache, nosebleeds and mild hair loss occurred in less than 10% of patients, and were self-terminating. Only in 4 patients (3%) was the treatment interrupted because of symptoms potentially related to vitamin A administration. As for laboratory tests, gamma-GT levels were abnormally elevated in 69% of treated patients vs. 39% of controls at 24 months (mean 149 vs. 58 IU/l; p less than 0.05). Serum triglyceride concentrations over 150 mg/dl were seen in 74% of treated patients vs. 43% of controls at 12 months (mean 283 vs. 179 mg/dl; p less than 0.05). There were no other laboratory signs of toxicity attributable to vitamin A. In our experience, high-dose retinoyl palmitate administration was a well-tolerated and safe treatment. The long-term impact on lipid metabolism still remains to be determined.