Randomized Trial Comparison of Ototoxicity Monitoring Programs

Research objectives are to compare the effectiveness of ototoxicity monitoring implemented
using Comp-VA or usual care with regard to (1) improving Veterans' hearing and quality of
life outcomes, (2) assisting oncologists in pre-treatment counseling and therapeutic planning
and (3) increasing use of post-treatment rehabilitative services.

The investigators plan to recruit a total of 320 Veterans undergoing cisplatin
chemotherapeutic treatment over 4 years and 120 control subjects.

Program Evaluation: Hearing testing prior to treatment will be done in order to establish
eligibility, enroll and randomize each subject into one of two study arms. At 5 weeks and at
one year post-randomization hearing will be re-tested in order to obtain an estimate of
longitudinal trends in hearing and quality of life assessment. Use of audiological services
following treatment from the randomized subjects will be tracked. Finally, data will also be
collected at each treatment interval to track use of counseling tools and oncology personnel
treatment decisions.

Serial measurements from subjects receiving cisplatin prior to treatment who are randomized
to:

Comp-VA group will get a screening hearing test prior to treatment, at each treatment
interval and at one-month post-treatment. Auditory testing will be done on or near the Chemo
Unit and will include otoscopy, immittance testing, and a hearing testing done by the Veteran
using a self-testing procedure, and may be tested using distortion product otoacoustic
emissions (DPOAEs), if they cannot take a reliable hearing test.

Usual care group will receive a full audiometric evaluation (otoscopy, immittance testing,
air conduction and bone conduction hearing testing, speech audiometry, and distortion product
otoacoustic emissions, DPOAEs) scheduled in the audiology clinic sound booth according to
Audiology Service ototoxicity monitoring protocols. Testing will be arranged according to
availability of appointments and patient convenience.

Additionally data will also be collected from control subjects who are similar in age and are
tested at intervals similar to the chemotherapy subjects.

Inclusion Criteria:

All Veterans entering cisplatin chemotherapy will be informed of the project and invited to
participate unless the Veteran was excluded by CPRS review or medical advice.

Exclusion Criteria:

- Experimental subjects must be prescribed cisplatin for treatment of cancer to be
enrolled in the treatment arms of this study.

Criteria for excluding subjects (chemotherapy and controls subjects) from this study will
be:

- cognitively or physically unable to participate (patient or nurse report patient is
incapable of participating), CPRS indication that subject exhibits aggressive
behavior, subject has documented dementia, Alzheimer's disease, or severe psychosocial
disorder, CPRS notes indicate individual is not legally capable of providing informed
consent (subject has a legal guardian)

- unable to provide reliable behavioral hearing test responses (for either program
evaluation hearing test or baseline, pre -treatment hearing test) as indicated by
intra-session behavioral threshold reliability criterion of > +5 dB)

- exhibits Meniere's disease or retrocochlear disorder based on hearing test results,
patient report or notes in CPRS

- exhibits active or recent history of middle ear disorder based on otoscopy,
tympanometry, patient report, or notes in CPRS

- unwilling to participate

- hearing thresholds > 70 dB SPL at 4 kHz and below (based on DPOAE 'no response' data
from a similar protocol described in Bibliography Reference 32, Table 3). The last
exclusion was adopted in an effort to increase the potential that DPOAEs will be
measurable in a large number of subjects.