1Ophthalmology Section, Department of Plastic Surgery; 2Department of Breast Medical Oncology; 3Department of Nuclear Medicine; and 4Department of Pharmacoeconomics, UT M.D. Anderson Cancer Center, Houston, TX, USA
Received 16 August 2001; accepted 27 August 2001.
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Abstract |
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The purpose of this study was to describe canalicular stenosis as a mechanism for epiphora (excessive tearing) secondary to weekly docetaxel.
Patients and methods
Fourteen patients with metastatic breast cancer who developed epiphora during weekly docetaxel therapy underwent an ophthalmologic examination, and probing and irrigation of the nasolacrimal ducts. The total duration of docetaxel therapy, the duration of treatment at the time of onset of epiphora, the number of infusions, the cumulative dose of docetaxel and the severity of canalicular stenosis were recorded.
Results
All 14 patients had anatomic narrowing of the canaliculi as the underlying mechanism for epiphora. Bicanalicular silicone intubation or dacryocystorhinostomy (DCR) was recommended for all 14 patients. Eleven patients underwent surgery and experienced resolution of their symptoms. The three patients who declined surgery continue to have epiphora at the time of this report.
Conclusions
Canalicular stenosis is an underlying mechanism for epiphora in patients receiving weekly docetaxel. Bicanalicular silicone intubation should be considered early in the course of weekly docetaxel therapy to prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, DCR with a permanent pyrex glass tube placement may become necessary to overcome the blockage of tear outflow.
Key words: bicanalicular silicone intubation, breast neoplasms, canalicular stenosis, docetaxel, epiphora, lacrimal apparatus diseases
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Introduction |
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Patients and methods |
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In each patient, the severity of canalicular stenosis as an anatomic finding was determined by one of us (B.E.) during in-office probing and irrigation using standard, previously published techniques and criteria [7]. All four canaliculi were evaluated in each patient. Moderate canalicular stenosis was defined as the presence of definite resistance when the probe was introduced into the canaliculi, but when the probe could be inserted all the way to a bony stop in the medial canthus. Severe canalicular stenosis was defined as inability to insert the metallic probe for the entire length of the canaliculus, in many instances, associated with severe pain or bleeding, or with total regurgitation of the irrigation fluid back through the canaliculus.
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Results |
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The mean cumulative dose of docetaxel at the time of diagnosis of epiphora was higher in patients with severe canalicular stenosis than in patients with moderate canalicular stenosis (P = 0.09; Table 3).
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Discussion |
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Canalicular stenosis associated with weekly docetaxel is most likely caused by secretion of docetaxel in the tear film and resultant chronic inflammation of the canaliculi due to direct contact with the drug as the tears travel through the canaliculi and the nasolacrimal duct to drain into the nose. Alternatively, the mucous membrane lining the canaliculi may become chronically inflamed and eventually fibrotic as part of the widespread mucositis caused by systemic absorption of docetaxel.
Although many patients who receive docetaxel once every 3 weeks experience transient symptoms of epiphora, we have not observed significant anatomic narrowing of the canaliculi in these patients (unpublished data). It is possible that administration of docetaxel on a sustained weekly schedule leads to more chronic exposure of the canaliculi to this drug. Furthermore, canalicular stenosis has not been reported with weekly administration of other taxanes. This raises the possibility that structural differences between docetaxel and other taxanes may make docetaxel more likely to be secreted in the tear film or more toxic to the canaliculi.
Five patients in our series were first diagnosed with canalicular stenosis as late as 30 weeks after cessation of therapy. It appears that once anatomic narrowing of the canaliculi secondary to docetaxel reaches a critical threshold, it is irreversible without appropriate surgical intervention.
Although most of the patients in this study received concurrent trastuzumab, we also observed canalicular stenosis in two patients who received weekly docetaxel as a single agent. Furthermore, the fact that docetaxel is associated with epiphora, albeit transient and mild, even when given every 3 weeks supports the notion that docetaxel and not trastuzumab is the causative agent for canalicular stenosis in patients reported in the current study. We are unaware of any previous reports of epiphora or canalicular stenosis secondary to the use of trastuzumab as a single agent.
The mean cumulative dose of docetaxel at the time of diagnosis was higher for patients with severe canalicular stenosis than for patients with moderate stenosis, although this difference was not statistically significant. This finding suggests that patients with advanced metastatic disease, who are likely to receive a longer course of weekly docetaxel and a higher cumulative dose, are at a greater risk of developing canalicular stenosis than patients who are exposed to a shorter course of this drug in the neoadjuvant setting.
Our study was not designed to assess quality of life issues in patients receiving weekly docetaxel. Nevertheless, it is important to note that every patient in this study sought consultation with an ophthalmologist because of epiphora, which they perceived as a visually disabling and bothersome symptom. They complained of inability to see because of excessive tearing and dissatisfaction with the misleading appearance of emotional tears secondary to canalicular obstruction. An analysis of quality of life measures in this cohort will be reported in a separate publication.
Although it is not possible to draw any conclusions from this retrospective case series with respect to the frequency of canalicular stenosis secondary to weekly docetaxel, our observations so far suggest that this side effect is fairly common in patients receiving weekly docetaxel for metastatic breast cancer. Burstein et al. [5] reported epiphora in 50% of 29 patients enrolled in a phase II trial of weekly docetaxel, although these authors were not aware of the underlying mechanism for this symptom. Future prospective studies are necessary to better define the frequency and timing of this side effect in patients receiving weekly docetaxel.
Given the recent widespread use of weekly docetaxel as an effective first- or second-line antineoplastic treatment for breast cancer and other common malignancies [4, 6, 912], it is crucial for ophthalmologists and oncologists to be aware of canalicular stenosis as a possible side effect of weekly docetaxel. Timely diagnosis of canalicular stenosis secondary to docetaxel and insertion of bicanalicular silicone stents can prevent complete closure of the canaliculi. Silicone tubes can be left in place until the patient is no longer exposed to docetaxel. Once complete closure of the canaliculi occurs, conjunctivodacryocystorhinostomy and placement of a permanent pyrex glass tube (Jones tube) is required to overcome the blockage of lacrimal outflow. We recommend referral to an ophthalmologist (ideally a lacrimal surgeon) at the earliest possible time after initiation of weekly docetaxel so that bicanalicular silicone intubation can be considered as soon as symptoms of epiphora are noted by the patient. Future prospective studies should focus on determining the frequency and timing of canalicular stenosis secondary to various schedules of administration of docetaxel and other taxanes.
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Footnotes |
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References |
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