A double blind randomized phase II study on the efficacy of topical eye treatment in the prevention of docetaxel induced dacryostenosis.

Abstract

Abstract Abstract #6144 Introduction: Weekly docetaxel, which is secreted in lacrimal tears, can cause dacryostenosis and eye tearing in up to 60% of patients. We hypothesized that eye drops containing corticosteroids may prevent the formation of fibrosis and hence stenosis of the lacrimal system. In addition, eye drops may wash out Docetaxel from the ocular surface and therefore decrease the occurrence of dacryostenosis. This study was designed to determine the efficacy of corticosteroid (CS) versus artificial tears (AT) topical eye treatment in patients on a weekly Docetaxel regimen.
 Patients and methods: Prospective, double-blind randomised, single-centre trial. Twenty patients who received a weekly Docetaxel (Doc) regimen for locally advanced or metastatic cancer, were enrolled. In a double blinded fashion, AT (Lacrystat®) were administered in one eye and dexamethasone sodium phosphate (CS)(Maxidex®) in the other eye, 6 times daily, from day 1 of cycle 1, continued throughout the Docetaxel administration, and stopped 2 weeks after the last Docetaxel administration. Before therapy and at week 3, 6 and 9, the patients were assessed for the following: watering, eye adnexes, irrigation and probing of the lacrimal drainage apparatus, and intra-ocular eye pressure. The primary endpoint was the incidence of dacryostenosis in each arm at 9 weeks in one eye treated with corticosteroid eye drops versus the other eye treated with artificial tears.
 Results: 1 pt with prostate cancer (Doc 36 mg/m2 qw 8w consecutively) and 19 pts with breast cancer entered the study (3 with LABC treated with Doc 36 mg/m2 d1-8 q3w plus capecitabine, +/- trastuzumab, 16 with metastatic BC treated with Doc 36 mg/m2 qw 8w consecutively). 9/20 eyes treated with CS and also 9/20 eyes treated with AT developed dacryostenosis at 9 week evaluation. Most cases of stenosis were grade 1 (narrowed punctum and/or canaliculus or impaired syringing of the outflow system after dilation of punctum) while only 2 eyes in CS and 1 eye in AT developed gr II stenosis (narrowed punctum impossible to dilate or narrowed canaliculus impossible to probe). Eye watering at week 9 was present in 9/20 eyes in CS (2 eyes discordant with stenosis) and 8/20 eyes in AT group (2 eyes discordant with stenosis).
 Conclusion: When prophylactic eye drops are administered during chemotherapy with weekly docetaxel, 45% of patients develop dacryostenosis after 9 weeks of docetaxel treatment. Although this study does not allow a comparison with a group without eye drops, the percentage of dacryostenosis in the eye drop group is quite high. There was no difference in the development of dacryostenosis in pts receiving corticosteroid or artificial tears (45% in both groups). This prospective double blind randomized phase II study does not confirm the hypothesis that eye drops containing corticosteroids prevent the formation of fibrosis and hence stenosis of the lacrimal system. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6144.