Low-Dose Thalidomide for Chemoprevention of Oral Leukoplakia: A Retrospective Observational Study

Oral leukoplakia (OLK) lacks effective chemopreventive treatments. Thalidomide, with anti-angiogenic, anti-inflammatory, and immunomodulatory effects, may influence OLK progression. This study assessed feasibility and preliminary biological effects of low-dose thalidomide on dysplasia and microvasculature.

A retrospective analysis was conducted on patients with OLK treated with thalidomide 50 mg/day for ≥ 30 days (2020-2024). The primary endpoint was change in dysplasia grade on paired biopsies. The secondary endpoint was change in intrapapillary capillary loop (IPCL) patterns on narrow-band imaging (NBI). Lesion size was also recorded. Adverse events (AEs) were graded using CTCAE.

Twenty-eight patients were included, most with moderate to severe dysplasia. No patient showed ≥ 50% lesion size reduction, and all maintained stable clinical size. Among 13 patients with paired biopsies, 38.5% showed histological improvement, while 30.8% showed progression. In 25 patients with NBI, 52.0% had improved IPCL patterns, while 32.0% remained stable, and 16.0% worsened. AEs were reported in 32.1%, most commonly peripheral neuropathy (14.3%), with no treatment discontinuations.

Low-dose thalidomide was feasible and well tolerated, showing biological activity by modulating dysplasia and IPCL patterns, despite minimal change in lesion size. These results support further prospective trials to confirm efficacy and refine treatment protocols.