Abstract
Abstract: :
Purpose: Docetaxel (Taxotere, Aventis, Bridgewater, NJ) is an effective antineoplstic agent widely used for the treatment of metastatic or locally advanced breast cancer as well as other malignancies. We have reported canalicular and nasolacrimal duct blockage as a side effect of weekly docetaxel. To test the hypothesis that canalicular stenosis may occur due to secretion of docetaxel in tears, we measured docetaxel concentrations in tears collected from 4 patients with metastatic breast cancer who received this drug. Methods: The experimental design was approved by the Institutional Review Board at the University of Texas M. D. Anderson Cancer Center. Two patients received every-three-week docetaxel at the dose intensity of 75 mg/m2. The other two patients received weekly docetaxel at 30 mg/m2 and 35 mg/m2 dose intensity, respectively.Tear fluid was collected from patients prior to infusion of docetaxel to serve as a control sample. An additional sample was collected within 30 min. following the end of docetaxel infusion. A drop of topical proparacaine was placed in each eye to achieve topical anesthesia. Polyester rods (America Filtrona Company, Richmond, VA) were placed in the inferior lateral conjunctival fornix. A bright light source was used to stimulate tear production. The polyester rod was then suspended in a microcentrifuge tube containing a shortened micropipette tip and frozen at - 70 °C. Tear fluid was subsequently recovered by centrifugation at 13,000 g at 4 ° C for 10-15 minutes. Drug concentration was determined in tear samples by direct injection of the fluid into a liquid chromatography instrument connected to a tandem mass spectrometer (Micromass Ultima LC/MS/MS, Beverly, MA). Results: Docetaxel was found in tear samples collected from all four patients. Docetaxel concentration in tears was dose dependent. Conclusion: Secretion of docetaxel in tears may be a possible mechanism for canalicular stenosis caused by docetaxel.
Keywords: 376 cornea: tears/tear film/dry eye • 390 drug toxicity/drug effects • 358 clinical laboratory testing