5-Fluorouracil for Treatment of Vocal Fold Scar

Vocal fold (VF) scar can result from trauma, neoplasm, inflammatory processes, congenital causes, surgery and other etiologies. In general, once the vibratory margin of the VF has been scarred, it has not been possible to return VF function to normal; but often it can be improved. The drug 5-fluorouracil (5-FU) is a pyrimidine antimetabolic that has many clinical applications ranging from systemic chemotherapy to topical treatment of actinic keratosis and basal cell carcinoma of the skin. Local injection with 5-FU also has been used for hypertrophic scar and keloids. 5-FU was shown to have benefit in animal models of VF scar and subglottic stenosis.

The present study aimed to evaluate the effect of 5-FU injection on VF vibratory function in patients with VF scar. Outcomes of 5-FU injection were compared to controls injected with dexamethasone.

Adult voice center patients who had undergone VF injection with dexamethasone or a series of three 5-FU injections for treatment of VF scar were included in the study. Postoperative outcomes included percentage of subjects demonstrating improvement after injection, change in scar size, glottic closure, and VF stiffness, as well as digital image analysis measurements of mucosal wave. Outcomes were compared between subjects who received 5-FU and those who received dexamethasone.

There were 58 VFs injected with 5-FU and 58 historical controls injected with dexamethasone. Baseline subject characteristics and etiology of scar did not differ significantly between the 5-FU and dexamethasone cohorts, except that scar size was greater in the 5-FU group and mucosal wave was worse at baseline. After a series of three 5-FU injections, 61.22% improved, 8.16% demonstrated no change, and 30.61% worsened. In the dexamethasone cohort, 51.06% improved, 0.00% demonstrated no change, and 48.94% worsened. The response differed significantly between the 5-FU and dexamethasone cohorts, with a greater proportion of subjects who underwent 5-FU injection demonstrating improvement postoperatively. In the 5-FU cohort, 32.76% of subjects previously had undergone and failed dexamethasone injection for VF scar: and within that group 84.21% improved, 5.26% demonstrated no change, and 10.53% worsened following 5-FU injection. On digital image analysis, the percent improvement in postoperative mucosal wave was significantly greater in the 5-FU cohort compared to the dexamethasone group, which demonstrated a worsening of mucosal wave.

A series of three intralesional injections with 5-FU outperformed dexamethasone for improving mucosal wave in patients with VF scar. A prior failed trial of dexamethasone injection predicted a favorable response to 5-FU. Further research is encouraged to confirm or refute these findings.