Risk of Ocular Adverse Events with Taxane Based Chemotherapy

ABSTRACT OBJECTIVE Taxane based chemotherapy agents such as docetaxel and paclitaxel are used for a wide range of cancers. Although much has been published on adverse events related to taxanes, data on ocular outcomes with these very important drugs is scant. We sought to quantify the risk of three ocular adverse events: 1) epiphora, 2) cystoid macular edema (CME) and 3) optic neuropathy with taxane based chemotherapy agents by undertaking a large pharmacoepidemiologic study. DESIGN New users, retrospective cohort study design SUBJECTS, PARTICIPANTS, CONTROLS We created a cohort of new users of women matched by age (within one year) on docetaxel or paclitaxel and new users of tamoxifen as controls. Study members were followed to the first incidence of the three outcomes. METHODS Descriptive statistics were used to examine demographics of the exposed and unexposed groups. A Cox model was constructed to compute crude and adjusted hazard ratios. Potential confounders for each outcome were adjusted for. MAIN OUTCOME MEASURES First diagnosis of 1) epiphora, 2) cystoid macular edema (CME) or 3) optic neuropathy ascertained using international classification for diseases 9 th or 10 th division codes. RESULTS For the epiphora analysis there were 1,824 taxane users (PTX or DTX) and 16,395 tamoxifen users. The crude HR for this association was 7.32 (95%CI: 4.25-16.61) and adjusted HR was 5.15 (95% CI:2.79-9.54). For the CME analysis there were 1,909 taxane user and 16,524 tamoxifen users. The crude HR for CME comparing taxane users to tamoxifen users was 1.37 (95% CI: 0.72-2.60) and adjusted HR was 1.33 (95% CI: 0.70-2.53). For optic neuropathy there were 1,913 taxane users and 16,566 tamoxifen users. The crude HR was 4.43 (95% CI:1.10-17.82) and the adjusted HR was 4.44 (95% CI:1.04-18.87). When we restricted our analysis to only cases of toxic optic neuropathy the aged-matched HR remained elevated (HR=7.24, 95% CI: 1.13-46.36). CONCLUSION In a cohort of women who were using taxane chemotherapy agents, there was an elevated risk for epiphora, optic neuropathy and a less precise increase in risk for cystoid macular edema. Ophthalmologists and oncologists should be aware of these adverse events in women with breast cancer who use these drugs.