Prevention of Docetaxel Induced Dacryostenosis

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

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.

Study Overview

• Status: Completed
• Conditions: Epiphora
• Intervention / Treatment: Drug: Maxidex; Lacrystat

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Mombaerts

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Lacrystat	Drug: Maxidex; Lacrystat; 6 times daily, for 20 weeks.
Active Comparator: Maxidex; Applying Maxidex	Drug: Maxidex; Lacrystat; 6 times daily, for 20 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dacryostenosis	20 weeks
Grading of dacryostenosis	20 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Ilse Mombaerts, MD, PhD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: December 16, 2005
• First Submitted That Met QC Criteria: December 16, 2005
• First Posted (Estimate): December 19, 2005

Study Record Updates

• Last Update Posted (Estimate): June 28, 2010
• Last Update Submitted That Met QC Criteria: June 24, 2010
• Last Verified: December 1, 2005

More Information

Terms related to this study

• Keywords: Epiphora; Lacrimal Obstruction
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: UZL OFT-ML 3386