This study sought to investigate the potential of 5-fluorouracil (5-FU) as an alternative treatment for odontogenic keratocysts (OKC) in the mandible. A total of 17 patients, diagnosed with non-syndromic and non-recurrent OKC, participated in this prospective and comparative clinical trial. All patients underwent enucleation and peripheral osteotomy of the cyst. Following this procedure, group A (n = 9) was treated with 5-FU, while group B (n = 8) received modified Carnoy’s solution (MC). The primary outcomes assessed included recurrence, nerve paresthesia, and bone healing. Statistical analysis for age, lesion size, gender, and location was performed using analysis of variance and the chi-square test. Kaplan-Meier analysis was used to use recurrence, and an unpaired t-test was used to compare bone healing. The patients’ ages ranged from 26 to 61 years, with a male-to-female ratio of 1.8:1. The follow-up period was 43.7 months for group A, and 47.5 months for group B. The 5-FU group showed no recurrence, while 25% of the MC group (n = 2) experienced recurrence. Kaplan-Meier survival analysis showed a 90% disease-free survival rate at 30 months for the MC group, which decreased to 70% at 60 months. Temporary nerve paresthesia was observed in 28.5% (n = 2) of the 5-FU group and 42.8% (n = 3) of the MC group, with all cases resolving completely. Bone healing, measured by changes in grey-level score, showed a mean increase of 36.52 ± 2.96 for the 5-FU group and 34.064 ± 6.52 for the MC group, with no significant difference between the groups (P = 0.225184). In summary, 5-FU proved to be a promising treatment for OKC, showing lower recurrence and nerve paresthesia rates compared to MC.
