Prospective Study of Ocular Adverse Events Induced By S-1

Abstract

ABSTRACT Aim: S-1 is an oral fluoropyrimidine agent and widely used for patients with various solid tumors in Asian countries. Few case reports and studies have documented common ocular adverse events including lacrimal canaliculus stenosis (LCS) and cornea epithelium disorder (CED) induced by S-1 administration. LCS causes watery eyes, blurred vision and photophobia, and CED causes vision disorder, as well as corneal ulcers which lead to blindness. Although these symptoms severely affect Quality of Life of cancer patients, the risk has not been clearly recognized by clinicians. We conducted a prospective study to investigate the incidence and severity of ocular adverse events induced by S-1. Methods: Patients who were candidates for S-1 were prospectively examined by 3 ophthalmologists to check their lacrimal canalicules and cornea epithelium before and every 4 weeks during administration of S-1 until cessation of the treatments. The patients underwent slit lamp biomicroscopic examinations to evaluate the incidence and severity of LCS and CED. Results: From December 2012 to December 2013, 40 patients were enrolled in this study (gastric cancer 23 patients, colorectal 8, pancreatic 4, lung 2, and other cancers 3). The ocular adverse events were detected in 17 patients (42.5%) in ophthalmic surveillance. LCS was seen in 13 cases (32.5%) and the median onset time of LCS was 99.6 days (21 to 274 days) after the initiation of S-1. Eight patients (20%) were diagnosed as grade 3 (CTCAE v4.0) and required needle dilatation of lacrimal canaliculus and 5 patients with severe symptoms of LCS needed insertion of drainage tubes in the lacrimal canaliculus. Seven cases (17.5%) were diagnosed as CED, of which 3 cases with grade 3 severe vision disorder required cessation of S-1 treatment. Corneal ulcers were detected in one patient. The mean onset time of CED was 112.7 days (42 to 331 days) after initiation of S-1. After cessation of S-1, recovery from all adverse effects was observed in all patients. Conclusions: This study showed a high incidence of ocular adverse events induced by S-1 treatment, with some patients suffering severe effects requiring ophthalmologic treatment. Oncologists should cooperate with ophthalmologists during S-1 treatment to prevent severe ocular adverse events by detecting disorders at an early stage. Disclosure: All authors have declared no conflicts of interest.