S-1-Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Studyopen access
- Authors
- Kim, Namju; Kim, Jin Won; Baek, Je-Hyun; Kim, Jin-Soo; Choung, Ho-Kyung; Kim, Tae-Yong; Lee, Kyung-Hun; Bang, Yung-Jue; Khwarg, Sang In; Ahn, Sang-Hoon; Park, Do Joong; Kim, Hyung-Ho; Chung, Jae-Yong; Ahn, Soyeon; Lee, Keun-Wook
- Issue Date
- Jan-2018
- Publisher
- KOREAN CANCER ASSOCIATION
- Keywords
- Lacrimal drainage obstruction; S-1; Fluorouracil; Tears; Stomach neoplasms
- Citation
- CANCER RESEARCH AND TREATMENT, v.50, no.1, pp 30 - 39
- Pages
- 10
- Journal Title
- CANCER RESEARCH AND TREATMENT
- Volume
- 50
- Number
- 1
- Start Page
- 30
- End Page
- 39
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/74832
- DOI
- 10.4143/crt.2016.569
- ISSN
- 1598-2998
2005-9256
- Abstract
- Purpose This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma. Materials and Methods A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma. Results Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (>= 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma >= 22.3 ng/mL (median), CDHP concentration in plasma >= 42.0 ng/mL (median), and tegafur concentration in tears >= 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1-related non-hematologic toxicity more frequently than those without LDO (p=0.016). Conclusion LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.
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