Tegafur and 5-fluorouracil levels in tears and changes in tear volume in long-term users of the oral anticancer drug S-1.

Abstract

ABSTRACTEye problems are an adverse reaction sometimes found in chemotherapy. Although not life-threatening, they can reduce patients’ quality of life. The highest incidence of eye problems is reported for the combination anticancer drug S-1 (tegafur–gimeracil–oteracil), and methods to prevent or treat the eye problems caused by this drug are presently lacking. To determine early detection methods and treatment for adverse ocular reactions, we measured changes in tear volume and levels of tegafur (FT) and 5-fluorouracil (5-FU), an active metabolite of FT, in the tears of patients with long-term use of S-1. A total of 11 patients receiving S-1 monotherapy as adjuvant chemotherapy after gastric cancer surgery were included. Tear volume and FT and 5-FU levels in tears were measured by liquid chromatography with tandem mass spectrometry during a maximum of 8 treatment cycles (48 weeks). For analysis, patients were divided into two groups: “watering eyes” (n=6, complaints of watering eyes at least once during the treatment period) and “no watering eyes” (n=5, no complaints of watering eyes). Both groups exhibited increased FT and 5-FU levels in tears upon initiation of S-1 treatment, and levels rapidly decreased upon discontinuation. Our findings suggest a relationship between FT level in tears and tear volume in patients with long-term S-1 use. The symptom of watering eyes may thus be linked to FT level in tears.