Prevention of Docetaxel Induced Dacryostenosis

This study has been completed.
Sponsor:
Information provided by:
Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier:
NCT00266838
First received: December 16, 2005
Last updated: June 24, 2010
Last verified: December 2005
  Purpose

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.


Condition Intervention Phase
Epiphora
Drug: Maxidex; Lacrystat
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
Official Title: A Double Blind Interventional Study of the Efficacy of Topical Eye Treatment in the Prevention of Docetaxel Induced Dacryostenosis

Resource links provided by NLM:


Further study details as provided by Universitaire Ziekenhuizen Leuven:

Primary Outcome Measures:
  • Incidence of dacryostenosis [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • Grading of dacryostenosis [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation Docetaxel in lacrimal tear and dacryostenosis [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2006
Study Completion Date: May 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Lacrystat
Lacrystat
Drug: Maxidex; Lacrystat
6 times daily, for 20 weeks.
Active Comparator: Maxidex
Applying Maxidex
Drug: Maxidex; Lacrystat
6 times daily, for 20 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00266838

Locations
Belgium
Mombaerts
Leuven, Belgium, 3000
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
Principal Investigator: Ilse Mombaerts, MD, PhD Universitaire Ziekenhuizen Leuven
  More Information

No publications provided

Responsible Party: Ilse Mombaerts, UZLeuven
ClinicalTrials.gov Identifier: NCT00266838     History of Changes
Other Study ID Numbers: UZL OFT-ML 3386
Study First Received: December 16, 2005
Last Updated: June 24, 2010
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Universitaire Ziekenhuizen Leuven:
Lacrimal Obstruction
Epiphora

Additional relevant MeSH terms:
Lacrimal Apparatus Diseases
Eye Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Docetaxel
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on July 31, 2014