Ocular complication induced by anticancer drug S-1: association with drug concentrations in tears.

Abstract

Purpose: S-1 is an orally active anticancer drug known to cause ocular adverse events (AEs), including lacrimal passage obstruction and corneal complications. This study investigated tear concentrations of 5-fluorouracil (5-FU) and tegafur (FT) in patients receiving S-1 treatment and their relationship with ocular AEs.

Study design: Multicenter prospective cohort study.

Methods: We recruited patients scheduled for S-1 chemotherapy. After initial ophthalmologic examinations at enrollment, serial examinations were performed during the courses of S-1 administration for up to 1 year. Tear samples were collected using Schirmer test strips at the end of the first course of S-1 treatment. 5-FU and FT concentrations were measured using high-performance liquid chromatography.

Results: The study cohort comprised 94 patients among whom 38 (40.4%) developed ocular AEs, including 32 (34.0%) corneal AEs, 13 (13.8%) lacrimal AEs, and 7 (7.4%) patients who developed both. The tear FT concentrations in the ocular AE group were significantly higher compared with the group without ocular AEs (3.15 ± 3.09 vs. 1.86 ± 1.56 µg/mL; p = 0.017). There was no difference in tear 5-FU concentration between the 2 groups. The FT concentration in tears in the corneal and lacrimal AE groups was significantly higher than in the group without ocular AEs (p = 0.013 and 0.030, respectively).

Conclusion: FT concentration in tears due to oral S-1 therapy is associated with corneal or lacrimal AEs. Measuring FT concentration in tears or plasma may be useful for predicting the onset of ocular AEs.