Hearing Loss and the Effects of Statin Drugs in People With Head and Neck Squamous Cell Carcinoma Treated With Cisplatin Chemoradiation

Objectives:

- Primary: Determine whether head and neck cancer patients taking statin drugs for
hyperlipidemia are at decreased risk of cisplatin-induced hearing loss.

- Secondary: Determine the incidence and severity of hearing loss in head and neck cancer
patients undergoing low-dose, weekly cisplatin chemotherapy with concurrent radiation.
Hearing loss with this more recent cisplatin regimen has not been thoroughly evaluated
in the literature. Examine whether age, gender, pre-existing hearing loss, other
medications, or comorbid medical conditions may be risk factors for cisplatin-induced
hearing loss and/or the acquisition or progression of tinnitus in this patient
population.

Study Population:

-Subjects will be adult patients with head and neck squamous cell carcinoma of the upper
aerodigestive tract who will undergo cisplatin chemotherapy with concurrent radiation.

Design:

- Observational study

- 334 subjects will be enrolled.

- Subjects will complete a questionnaire to estimate the degree of prior noise exposure
and impact on baseline hearing. Information on medical comorbidities, names and doses of
current medications will be obtained from the medical record and verified at each
subject visit.

- Subjects will complete self-administered audiograms using FDA-approved software from
SHOEBOXTM Audiometry on a portable tablet (iPad) computer.

- Audiograms will be completed prior to commencing chemoradiation, within 4 weeks of
completing treatment, and 6 months after completing treatment.

- Subjects will also complete a validated tinnitus questionnaire with each audiogram. A
noise exposure history will be collected during the initial study visit and verified
during subsequent visits. Any indicated changes to the subject s noise exposure history
will be added to record.

- No investigational or experimental therapy will be given as part of this protocol.

- Audiograms will be performed at the Johns Hopkins Suburban Outpatient Center or the NIH
Clinical Center.

- Two interim analyses will be conducted prior to study completion (after N=88 and N=176
subjects completing the protocol) to determine whether there are statistically
significant differences in severity or incidence of hearing loss in subjects taking
concurrent statin drugs vs. subjects who are not taking statin drugs.

Outcome Measures:

- Primary outcome measure: The primary outcome measure is the change in hearing
sensitivity (as measured by the self-administered audiogram) between the pre-treatment
(before cisplatin therapy) hearing test and the post-treatment (after completion of
cisplatin therapy) audiogram. Hearing loss will be defined according to TUNE and ASHA
criteria and will be compared in subjects taking statin drugs vs. subjects not taking
statin drugs. Hearing status will be compared between audiograms collected at baseline
(prior to treatment) to a repeated audiogram at the end of treatment (within 4 weeks of
cisplatin protocol cessation).

- Secondary outcome measure: Secondary outcome measures include 1) changes in hearing
sensitivity between the first post-cisplatin audiogram and the second post-cisplatin
audiogram, and 2) changes in scores on the tinnitus questionnaire between the
pre-treatment audiogram and the two post-treatment audiograms.

- INCLUSION CRITERIA:

- Adult patients over the age of 18.

- Patients with squamous cell carcinoma of the upper aerodigestive tract including the
larynx, hypopharynx, oropharynx, and oral cavity who undergo treatment with
concomitant cisplatin chemotherapy and intensity-modulated radiotherapy (IMRT) with
curative intent.

- Patients treated with cisplatin chemoradiation either as primary/definitive or
adjuvant (post-surgical) therapy.

- Subjects must be able and willing to self-administer their hearing test via the iPad
following a brief tutorial with one-on-one instruction from a member of the study team
or medical staff.

- Subjects must have hearing thresholds at or better than 80 dB SPL at 1, 2, and 4
kilohertz (kHz) at the time of their baseline audiogram.

- Subjects must have a Type A tympanogram.

- Subjects must be able to provide their own consent.

EXCLUSION CRITERIA:

- Patients with carcinoma of the nasopharynx or paranasal sinuses, who may have
Eustachian tube dysfunction (with resultant conductive hearing loss) related to
radiation treatment involving these anatomic subsites.

- Patients with active middle ear disease that is likely to influence the results of
audiograms during the study, as determined by an Investigator who is an
otolaryngologist. If a potential subject reports active middle ear disease, medical
records will be reviewed by a study otolaryngologist to determine whether the patient
should be excluded.

- Patients with cochlear implants will be excluded.

- Patients with a history of prior treatment with platinum chemotherapy drugs will be
excluded.

- Patients who receive taxanes or other cytotoxic chemotherapy drugs in addition to
cisplatin will be excluded. The standard of care is cisplatin as monotherapy for
previously untreated HNSCC.

- Staff members of the NIDCD Sections that are headed by the PI and LAI will be
excluded.