Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia

BACKGROUND It has been previously observed that patients with head and neck squamous cell carcinoma or with laryngeal leucoplakia present a significant reduction in plasma folate levels. The current Phase IIA pilot study assessed the effectiveness of folic acid as a chemopreventive agent in patients affected by glottic laryngeal leucoplakia, METHODS Forty‐three untreated patients affected by glottic laryngeal leucoplakia were enrolled in the Ear, Nose, and Throat Department (Universita Cattolica del Saco Cuore, Rome, Italy). Glottic leucoplakia was initially diagnosed by indirect laryngoscopy and successively confirmed by diagnostic direct microlaryngoscopy with a biopsy for histologic assessment. Folic acid (Folina, Schwarz Pharma, Germany) was administered orally (5 mg every 8 hours) for 6 months. Patients were monitored every 30 days by videolaryngoscopy. RESULTS Twelve (28%) patients had no response, 19 (44%) had a partial response, and 12 (28%) had a complete response. The mean increase in serum folate levels (10.06 ± 0.53) and the mean decrease in homocysteine serum (3.65349 ± 0.85526) at the end of the study were highly significant (P = .0001). CONCLUSIONS The larynx is 1 of the sites of major interest and a good model for the development of chemopreventive agents, but so far the proposed agents have shown no clear efficacy on precancerous lesions or on the development of second malignancies. Cancer 2006. © 2006 American Cancer Society. The current results suggest the hypothesis that folate insufficiency is a long‐term risk factor that increases the rate of carcinogenic progression after exposure to environmental carcinogens. The present pilot chemopreventive study seems encouraging, with a complete response rate of 27% and no clinical or histologic progression of leucoplakia after a 6‐month treatment.