Epiphora in lung cancer patients receiving docetaxel: a case series

Docetaxel is a highly effective chemotherapeutic agent for non-small cell lung cancer (NSCLC) [1]. Common adverse events are neutropenic fever, anemia, fluid retention, hypersensitivity reactions, anorexia, myalgia, mucositis, alopecia, skin and nail toxicity, and peripheral neuropathy [2]. Epiphora (excessive tearing) was reported to occur in up to 64% of breast cancer patients receiving docetaxel-based chemotherapy [3]. It has been suggested that tearing may result from canalicular and nasolacrimal duct stenosis [4]; however, Chan et al. [5] reported that epiphora was not necessarily caused by lacrimal duct obstruction in breast cancer patients receiving adjuvant docetaxel-based combination chemotherapy. Although docetaxel is a key antineoplastic drug for NSCLC treatment, there have been few reports regarding epiphora in patients with NSCLC. Here, we report three NSCLC patients who developed epiphora after the administration of docetaxel-based chemotherapy.

We experienced three patients with advanced NSCLC who developed epiphora after the administration of docetaxel-based chemotherapy. Common ocular toxicities associated with docetaxel administration include epiphora and conjunctivitis [7]. Chan et al. [5] reported that the incidences of tearing and other eye symptoms associated with docetaxel-based treatment was 86%, suggesting that epiphora was one of the most common adverse events. Excessive tearing interferes with daily life activities such as driving, reading, and visual tasks. The frequency and severity of epiphora increased with weekly administration of docetaxel compared with administration every 3 weeks [8]. In addition, ocular toxicity occurred in patients receiving a median or mean cumulative docetaxel dose of 300 or 400 mg/m² or a higher dose [9]. Cumulative doses of docetaxel in our cases were all more than 500 mg/m². The relations of the patients’ docetaxel exposures to expected incidence rates were prospectively analyzed [5]. There was a trend for lower rates of tearing in patients receiving lower cumulative doses of docetaxel. However, we should be aware that the combined drug with docetaxel such as fluorouracil can affect the rates.

Canalicular stenosis associated with 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 [4, 9, 10]. Importantly, epiphora occurs either with or without the presence of lacrimal duct obstruction [5], the latter being considered reactive tearing to ocular dryness [11]. Mild to moderate epiphora may resolve without medical or surgical intervention after discontinuation of docetaxel [4]. However, delayed recognition and management of this adverse event can lead to severe lacrimal duct obstruction that cannot be managed with silicon intubation and requires more complicated surgery [4]. The use of eye drops such as artificial tears may wash out docetaxel from the ocular surface and thereby prevent the development of dacryostenosis [11].

Epiphora associated with the treatment using other taxane, paclitaxel, seems to be rare. A patient who was treated with paclitaxel for angiosarcoma of the head and neck developed epiphora [12]. A phase III study comparing the efficacy of docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer showed that grade 3 and 4 tearing was reported in 5% of patients who received weekly docetaxel versus less than 1% of patients who received docetaxel once every 3 weeks, weekly paclitaxel, or paclitaxel once every 3 weeks [13]. The study also revealed that grade 2 tearing occurred 19%, 5%, 1% and 1%, respectively. In addition, ocular toxicities in NSCLC treated with paclitaxel did not include epiphora [7]. In terms of similar effectiveness of the two taxanes for NSCLC, a patient receiving docetaxel with toxicity of epiphora may change the chemotherapeutic drug to paclitaxel.

Excessive tearing in our three cases improved gradually with timely diagnosis and management. One patient with mild punctal stenosis was improved by probing and irrigation. In the other two patients, epiphora was resolved by discontinuation of docetaxel or use of artificial tears. When the symptoms do not resolve, epiphora has a substantial negative impact on the patient’s quality of life. Our experience with patients who have developed epiphora suggests that ophthalmological examination and careful monitoring during docetaxel treatment may lead to successful management and reduced ocular toxicity.

In conclusion, it is important for oncologists to be aware of this adverse event, and ophthalmologists should be consulted in cases in which tears appear during docetaxel therapy.

Written informed consent was obtained from the patients for publication of this Case Report and any accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal.