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Cancer Res Treat. 2018 Jan;50(1):30-39. doi: 10.4143/crt.2016.569. Epub 2017 Feb 27.

S-1-Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study.

Author information

1
Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
2
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
3
Center of Biomedical Mass Spectrometry, Diatech Korea Co., Ltd., Seoul, Korea.
4
Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
5
Department of Ophthalmology, Seoul National University Boramae Medical Center, Seoul, Korea.
6
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
7
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea.
8
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
9
Department of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
10
Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.

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.

KEYWORDS:

Fluorouracil; Lacrimal drainage obstruction; S-1; Stomach neoplasms; Tears

PMID:
28253565
PMCID:
PMC5784617
DOI:
10.4143/crt.2016.569
[Indexed for MEDLINE]
Free PMC Article

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