Prevention of Docetaxel Induced Dacryostenosis

Study Overview
=================
Brief Summary
-----------------
The antineoplastic agent Docetaxel (Taxotere®) is approved for the treatment of patients with metastatic and locally advanced breast cancer and other malignancies. There are 2 frequently used schedules of treatment with Docetaxel. Docetaxel can be administered every 3 weeks or in a weekly regimen. The efficacy seems to be similar but the toxicity profile changes. In the standard 3-weekly Docetaxel regimen the dose-limiting side effect is myelosuppression, while in the weekly regimen there is only a mild myelosuppression. On the other hand, weekly Docetaxel has a side effect that is rare in the 3-weekly schedule: epiphora (= tearing eye) caused by dacryostenosis. The underlying mechanism of dacryostenosis induced by weekly Docetaxel is fibrosis of the lacrimal puncta and canaliculi. Docetaxel has been reported to be secreted in the lacrimal tears. Direct contact between Docetaxel containing tears and the epithelial lining causes chronic inflammation of the mucosa and ultimately fibrosis of the most narrow part of the lacrimal outflow system i.e. the lacrimal puncta and canaliculi. A surgical treatment is possible for dacryostenosis. In case of subtotal stenosis of the lacrimal canaliculi, silicone intubation of the canaliculi is performed in order to prevent further closure. In the case of complete stenosis, placement of a permanent pyrex glass tube of Jones is required. To our knowledge, there is no primary prevention for Docetaxel induced dacryostenosis. The rationale of this randomized double blind interventional study is to investigate the efficacy of corticosteroid versus artificial tears topical eye treatment in patients on a weekly Docetaxel regimen in prevention of dacryostenosis. The dacryotoxic agent Docetaxel in the lacrimal tears will be washed away by the repetitive use of eye drops. In addition, eye drops containing corticosteroids have an anti-inflammatory effect and may further prevent the formation of fibrosis. A new treatment protocol will be investigated. Two different commercially available eye drops will be compared: dexamethasone sodium phosphate (Maxidex®, Alcon) in one eye of the patient and artificial tears (Lacrystat®, Viatris) in the other eye of the same patient. The study period will start with topical eye treatment from day 1 of cycle 1 and will continue during the administration of chemotherapy, with a final analysis at 26 weeks.

Official Title
-----------------
A Double Blind Interventional Study of the Efficacy of Topical Eye Treatment in the Prevention of Docetaxel Induced Dacryostenosis

Conditions
-----------------
Epiphora

Intervention / Treatment
-----------------
* Drug: Maxidex; Lacrystat


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with locally advanced or metastatic breast cancer receiving weekly Docetaxel chemotherapy with rest weeks in between at regular time intervals. The timing of rest weeks between cycles is not restricted. Examples of allowed regimens are Docetaxel 36 mg/m2 day 1 and 8 every 3 weeks; day 1, 8, 15 every 4 weeks; day 1, 8, 15, 21, 28, 35, 42, 49 every 10 weeks. Dosing and rest weeks can be further modified depending on the clinical situation, but dose intensity should be at least 60 mg/m2 every 3 weeks during the 9 week treatments for eligibility. Combination with other chemotherapy (such as capecitabine) is allowed. Capability to administer eye drops (either by patient or companion). Written informed consent. Age > 18 y Exclusion Criteria: Systemic criteria: Previous administration of Docetaxel. Pregnancy. Eye criteria: Ocular surface, corneal, conjunctival or eyelid disease. Soft contact lens wearing Glaucoma Lacrimal criteria: Hypersecretion of tears: ocular surface, corneal, conjunctival or eyelid disease. Functional blockage of lacrimal drainage without anatomical obstruction (facial nerve palsy, displacement of the lower lacrimal punctum from the lacrimal lake, involutional lower eyelid laxity). Anatomical obstruction of lacrimal drainage system:

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Lacrystat<br>Lacrystat | Drug: Maxidex; Lacrystat<br>* 6 times daily, for 20 weeks.<br>|
| Active Comparator: Maxidex<br>Applying Maxidex | Drug: Maxidex; Lacrystat<br>* 6 times daily, for 20 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dacryostenosis |  | 20 weeks | 
| Grading of dacryostenosis |  | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Docetaxel in lacrimal tear and dacryostenosis |  | 20 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lacrimal Obstruction, Epiphora