s-1-(combination) and Eye-Diseases

S-1 is an oral antineoplastic agent containing tegafur, gimeracil, and oteracil potassium. Recently, ophthalmic disorders, particularly epiphora, have been reported. We retrospectively investigated the incidence of ophthalmic disorders in patients treated with a regimen containing S-1 at our institution. Ophthalmic disorders were noted in 28 of 261 patients(10.7%). These included epiphora(17 cases), eye discharge(10 cases), conjunctivitis(6cases ), blurred vision(3 cases), and eye discomfort(2 cases), as well as eye pain, pruritus, dry eye, hordeolum, and visual loss(1 case each). The median time from starting treatment to appearance of the condition was 3.0(interquartile range 1.5-4.5)months and the median cumulative S-1 dose was 4.2(interquartile range 2.2-9.5)g. More men than women developed ophthalmic disorders on S-1. The median total dose and duration of treatment were higher in those developed ophthalmic disorders than in those who did not (12.4 g vs 6.3g and 8.6 months vs 4.4 months). Epiphora was the most common of a number of ophthalmic disorders seen in our patients treated with S-1. Patients and physicians should be fully informed of the potential association between S-1 and ophthalmic disorders, and patients receiving this treatment need to be carefully monitored.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Eye Diseases; Female; Humans; Incidence; Male; Middle Aged; Neoplasms; Oxonic Acid; Retrospective Studies; Tegafur

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Eye Diseases; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

To elucidate the features of optic lesions in patients with epiphora during S-1 therapy.. Twelve patients with epiphora in 123 patients during S-1 therapy.. Age range was 38-84 years (mean 68.4 years). There were 4 cases in 81 men (5%) and 8 in 42 women (19%). Epiphora occurred significantly more often in women (p=0.02). The administration period was from 10 days to 36 months. Lesions were superficial punctate keratopathy in 10 cases with cornea and obstruction of inferior punctum in 2, stenosis of nasolacrimal duct in 1 and suspected occlusion of the nasolacrimal duct in 1 with lacrimal duct. Local therapy was eye drops in all cases. Of the whole 12 patients, S-1 was continued or discontinued in 6 each of all 12 cases, in 5 each of 10 cases with superficial punctate keratopathy, and in 2 each of 4 cases with lacrimal duct lesions. Epiphora/optic lesions improved with a range from 10 days to 1.5 months in cases of discontinuation and with that from 2 weeks to 1 month in cases of continuation.. Our results revealed superficial punctate keratopathy in many cases, lacrimal duct lesions in a few cases, and discontinuation of medication provided improvement of optic events.. When epiphora is observed in patients on S-1 therapy, it is necessary to assess optic disorders by an opthalmologist immediately because of suspicion of injury to the cornea and lacrimal duct.

Topics: Adult; Aged; Aged, 80 and over; Drug Combinations; Eye Diseases; Female; Humans; Lacrimal Apparatus Diseases; Male; Middle Aged; Neoplasms; Oxonic Acid; Tegafur

S-1 is an oral antineoplastic agent that contains a prodrug of 5-fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the ocular surface. We investigated the effects of S-1 on the corneal epithelium by in vivo confocal microscopy and histopathologic analysis.. Twelve patients with eye problems related to S-1 treatment participated in the study. Twenty eyes of ten subjects were evaluated by laser-scanning confocal microscopy. Corneal epithelial debridement as a diagnostic therapy and histopathologic analysis were performed for five eyes of three subjects affected in the pupillary zone of the cornea.. Slitlamp examination revealed a local limbal abnormality characterized by epithelial invasion toward the center of the cornea in all 24 eyes. In vivo confocal microscopy revealed an altered structure of the corneal epithelium with abnormal epithelial cells and inflammation. One of five specimens subjected to cytologic diagnosis showed moderate dysplasia. Hematoxylin and eosin staining showed that each abnormal epithelial sheet lacked the stratified structure of the normal corneal epithelium. Immunofluorescence analysis revealed the presence of cells positive for one, both, or neither of cytokeratins 12 and 4 in each lesion.. S-1 can induce ocular mucositis with dysplasia, likely affecting cellular functions, including differentiation, of the corneal epithelium. In vivo confocal microscopy allowed the noninvasive detection of cellular changes in the cornea as an adverse effect of S-1 administration.

Topics: Aged; Antineoplastic Agents; Drug Combinations; Eye Diseases; Female; Humans; Inflammation; Male; Microscopy, Confocal; Middle Aged; Mucositis; Oxonic Acid; Tegafur

52-week oral repeated-dose S-1 toxicity studies were conducted. Male and female dogs were orally treated with 0, 0.1, 0.5 or 2.5 mg/kg/day for 52 weeks and permitted to recover for 13 weeks. Furthermore, to estimate the no-toxic dose, male and female dogs were given S-1 orally for 52 weeks at doses of 0, 0.004 and 0.02 mg/kg/day. The 2.5 mg/kg/day regimen produced one dead or moribund dog of each sex; black-brown patch (melanin deposition) and inflammatory changes in the eyes and skin; decreased in body weight gains; increases in MCV, MCH, monocyte ratio, and serum protein and uric acid; decreases in lymphocyte ratio and erythrocyte count, hematocrit, hemoglobin, albumin, A/G ratio, cholesterol (esterified, total and free), phospholipids, triglycerides, cholinesterase activity and creatinine; increases in relative liver and adrenal weights. Histopathological examinations revealed melanin deposits in superficial lymph nodes, increases in macrophage and plasma cell accumulation, and corneal atrophy accompanied by melanin deposits and capillary proliferation. A slight black-brown patch (melanin deposition) in the conjunctiva and skin was observed in the 0.1 and 0.5 mg/kg/day groups. No drug-related changes were observed in groups that received 0.02 and 0.004 mg/kg/day. All changes observed during the treatment period disappeared during recovery except for melanin deposits in the conjunctiva and superficial lymph nodes, corneal opacity, and a few hematological and blood chemistry parameters. In conclusion, the no-toxic dose in these 52-week studies was estimated to be 0.02 mg/kg/day.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Blood Chemical Analysis; Blood Coagulation; Body Weight; Dogs; Drug Combinations; Eye; Eye Diseases; Female; Hematologic Tests; Hyperpigmentation; Lymph Nodes; Male; Organ Size; Oxonic Acid; Pyridines; Skin; Skin Diseases; Tegafur; Urinalysis