Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment
Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignant neoplasms, including testicular, ovarian, bladder, cervix uteri, head and neck and lung cancers.
One of the common side-effects of this drug is bilateral, symmetric, progressive and usually irreversible sensorineural hearing loss.
Cisplatin induces cochlear toxicity by the production of reactive oxygen species (ROS).
Dexamethasone treatment is currently practiced for various pathologies afflicting the inner ear. The positive effect of Dexamethasone is attributed to it's anti ROS activity and it's capability to up-regulate cochlear anti ROS enzymes.
In order to reach higher inner ear concentration of the drug while avoiding it's undesirable systemic side-effects, Intratympanic (IT) delivery of Dexamethasone became vastly used in the last decades for the treatment of sudden sensorineural hearing loss and Meniere's disease.
Dexamethasone inserted IT, diffuse across the round window into the inner ear perilymph where it exerts its therapeutic effects.
The investigators review of the literature yielded three animal studies which examined the protective effect of IT dexamethasone in the prevention of cisplatin-induced hearing loss. These studies demonstrated promising results pointing to the potential for IT dexamethasone in the prevention of cisplatin ototoxicity in humans.
The purpose of this study is to examine possible protective effect of IT dexamethasone on cisplatin-induced hearing loss, in humans.
The study hypothesis is that IT dexamethasone treatment would prevent cisplatin-induced hearing loss.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Prevention of Cisplatin-Induced Hearing Loss by Intratympanic Dexamethasone Treatment.|
- Examine possible protective effect of IT dexamethasone on cisplatin-induced hearing loss. Hearing assessment would include:pure tone, speech and impedance audiometry, and Distortion Product Otoacoustic Emissions (DPOAEs) testing. [ Time Frame: Two years ] [ Designated as safety issue: No ]Distortion Product Otoacoustic Emissions (DPOAEs) testing is a test that specifically evaluates the functioning of the cochlear outer hair cells which are the primary target organ for cisplatin ototoxicity.
|Study Start Date:||June 2011|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Drug: Dexamethasone Phosphate
0.7ml of Dexamethasone Phosphate 10mg/ml would be injected unilaterally to the middle ear using 25 gauge spinal needle.
The trans-tympanic membrane injection would take place at the posterior inferior quadrant of the ear drum facing the round window niche. The patient would be instructed to lie down for 20 minutes after the injection with the treated side up and to avoid swallowing or coughing. Intratympanic Dexamethasone would be delivered immediately prior to each cisplatin treatment as maximal level.
Other Name: Decadron, Dexamethasone Intensol, Dexpak Taperpak, Zema Pak
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01372904
|Clalit Health Services|
|Principal Investigator:||Tal M Marshak, MD||Clalit Health Services|