Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy

Kim, N.; Park, C.; Park, D. J.; Kim, H. H.; Kim, S.; Kim, Y. J.; Kim, J. H.; Lee, Ji Su; Bang, Yung‐Jue; Khwarg, Sang In; Choung, Ho Kyung; Lee, M. J.; Lee, K. W.

doi:10.1093/annonc/mds106

Cited by 28 publications

(48 citation statements)

References 31 publications

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“…Kim et al [11] reported low creatinine clearance (\50 mL/min) as a risk factor for lacrimal duct complications because gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades 5-FU) is mainly excreted in the urine, and renal dysfunction leads to a sustained high plasma concentration of 5-FU. All of the patients in our study had normal renal function at day 30 (median time to onset of ocular complications caused by S-1).…”

Section: Discussionmentioning

confidence: 99%

“…S-1 is prescribed for either 10 or 12 months as postoperative adjuvant chemotherapy for gastrointestinal cancer; it is also used for 2 or 3 years for treating advanced gastric cancer. The agent induces inflammation [12], and chronic inflammation leads to disruption of the normal layered structure of the epithelium, a decline in corneal transparency and smoothness, and lacrimal duct blockage [11]. Changes to the corneal epithelium and lacrimal duct complications lead to visual disturbances.…”

Section: Discussionmentioning

confidence: 99%

“…After administration, 5-FU rapidly reaches a high serum concentration that is maintained for a long time [3], which can lead to complications in sensitive tissues and organs [4]. Myelosuppression, diarrhea, stomatitis, and skin pigmentation are some of the major complications caused by S-1 [5][6][7][8], but ocular complications, such as corneal damage [superficial punctate keratitis (SPK), sheet-like appearance, epithelial erosion, epithelial crack lines], lacrimal duct blockage, and conjunctivitis have also been reported [9][10][11][12]. Complaints such as lacrimation, eye pain, visual disturbances, and difficulties in opening the eyes due to discharge or foreign body sensation, are recurring ocular complications of S-1 chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Predictive factors for ocular complications caused by anticancer drug S-1

et al. 2016

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Predictive factors for ocular complications caused by anticancer drug S-1

et al. 2016

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“…The incidence of watering eyes was 16 % in a phase III trial conducted in Japan for metastatic AGC which involved S-1 monotherapy [2]. There have been some reports [8][9][10][11][12][13][14][15] focusing on watering eyes; however, these studies included a small number of patients and S-1 combination chemotherapy in a palliative setting, and the contribution of the ophthalmologists was not clear. This study included more than 300 AGC patients treated with adjuvant S-1 monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, previous reports about watering eyes [8][9][10][11][12][13][14][15] have included a small number of patients whose characteristics and chemotherapy regimen differed.…”

Section: Introductionmentioning

confidence: 99%

Excessive watering eyes in gastric cancer patients receiving S-1 chemotherapy

et al. 2015

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Background Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known. Methods This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes. Results The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m 2 (range 491-16,095 mg/m 2 ) and 10,243 mg/m 2 (range 4943-16,341 mg/m 2 ), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes. Conclusion The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.

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Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients

et al. 2019

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Background S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies have been reported on watering eyes caused by S-1. However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study was to investigate the correlation between tears and plasma concentrations of FT, 5-FU, and CDHP, which are components and active modulator of S-1. Methods We prospectively investigated the pharmacokinetics (PK) of FT, 5-FU, and CDHP in plasma and in tears of gastric cancer patients who were treated with S-1 monotherapy at the dose of 80 mg/m 2 /day. Plasma and tears from both eyes were obtained 1, 2, 4, and 8 h after S-1 administration on day 1 and 14 of the first cycle. Results Total of eight patients were enrolled. All the FT, 5-FU and CDHP were detected both in plasma and in tears, and their PK parameters were measured. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears on day 1 and day 14 (correlation coefficients r , right eye/left eye: r = 0.882/0.878, 0.877/0.890, and 0.885/0.878, respectively). Conclusion There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears. The result is expected to facilitate the further investigation into the causes of watering eyes and the establishment of the effective methods for the prevention and the treatment.

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Lacrimal drainage obstruction in gastric cancer patients receiving S-1 chemotherapy

Cited by 28 publications

References 31 publications

Predictive factors for ocular complications caused by anticancer drug S-1

Predictive factors for ocular complications caused by anticancer drug S-1

Excessive watering eyes in gastric cancer patients receiving S-1 chemotherapy

Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients

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