International Journal of Otorhinolaryngology and Head and Neck Surgery

Sivasankari L et al. Int J Otorhinolaryngol Head Neck Surg. 2018 Sep;4(5):1297-1300

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DOI: http://dx.doi.org/10.18203/issn.2454-5929.ijohns20183705
Original Research Article

A study of cisplatin chemotherapy and hearing loss

L. Sivasankari1*, Lalitha Subramanian2
1
Department of ENT, Kanyakumari Medical College, Tamil Nadu, India
2
Department of Oncology, Thoothukudi Medical College, Tamil Nadu, India

Received: 24 June 2018

Revised: 05 August 2018
Accepted: 06 August 2018

*Correspondence:
Dr. L. Sivasankari,
E-mail: [email protected]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Various medications have been associated with ototoxicity. Platinum containing chemotherapeutic
agents are associated with cochleotoxicity, characterized by high frequency hearing loss. Cisplatin and related agents
are absorbed by the cochlear hair cells, resulting in ototoxicity through the production of reactive oxygen species.
Methods: About 67 patients, irrespective of the type of cancer, fit to undergo chemotherapy were considered for
study after meticulous examination. Audiograms were taken prior to chemotherapy, at the end of each cycle of
chemotherapy, and follow-up audiograms at 3 months and 6 months after completion of chemotherapy.
Results: Among 37% of the patients with normal hearing, 10% of the patients developed sensorineural hearing loss
after treatment. Among 63% of the patients with prior mild sensorineural hearing loss, 11.8% developed worsening of
hearing after completion of treatment.
Conclusions: Audiologic monitoring is important in patients undergoing cisplatin chemotherapy and post-
chemotherapy auditory monitoring is essential to rehabilitate the patients with Sensorineural hearing loss.

Keywords: Cisplatin chemotherapy, Ototoxicity, Sensorineural hearing loss

INTRODUCTION ototoxicity. As hearing loss after completion of

chemotherapy are inevitable, patients getting
Chemotherapy drugs such as cisplatin are commonly chemotherapy with cisplatin needs Hearing rehabilitation.
used to treat several types of cancer. While chemotherapy
has saved many lives, an unfortunate side effect can be Cisplatin is used for treatment of solid tumours like
ototoxicity, causing bilateral, progressive and permanent ovarian, testicular, cervical, lung, head and neck and
sensorineural hearing loss. Cisplatin is mainly bladder cancers. Cisplatin is a cell cycle – nonspecific
cochleotoxic, affecting the outer hair cells first producing cytotoxic drug and has a toxic profile different from other
an oxidative stress. The hearing loss usually start with cytotoxic agents. High doses of cisplatin cause
high frequencies, so it is not immediately obvious to the nephrotoxicity, gastro-intestinal toxicity, neurotoxicity
patient. As the chemotherapy treatment continues, the and ototoxicity. Ototoxicity is one of the dose – limiting
hearing loss become more severe and affects wider range side effects of cisplatin, it increases with increase in dose.
of frequencies. When the speech frequency range is It shows higher inter-individual variability.1 The etio-
affected, patients may require amplification with hearing pathogeneis of this inter-individual variability is
aids after completion of chemotherapy. Even though unknown, but pharmacokinetic differences, genetic
many drugs amifostine, vitamin E, N– acetyl cysteine, factors and metabolic status of the individuals has been
anti- inflammatory and anti-oxidant drugs have been used implicated.2 Identification of the susceptible individuals
as trial, none appear to be a novel drug to prevent from before treatment is not possible, however early ototoxic

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effects can be detected by serial audiometry, and it helps 3 patients had carcinoma of larynx. Among 54 patients,
in early management of these patients. 22 patients were in stage III, accounting to about
maximum of 40.74%. 21 patients in stage IV, accounting
METHODS to about 38.8%, 9 patients in stage II, resulting for 16.6%
and 2 patients in stage I, resulting for 3.7%.
A prospective study was conducted in the Department of Pathologically, 17 patients had grade II, 12 patients had
ENT in Thoothukudi Medical College for a period of one grade III and 11 patients had grade I tumours.
year (January 2016 to December 2016). Around 67 Histopathologically, 30 patients with lung, oesophagus,
patients between the age group of 15–80 years of age, stomach and pancreas tumours were adenocarcinoma, 19
irrespective of the type of cancer, fit and eligible to patients were squamous cell carcinoma and invasive
undergo chemotherapy with cisplatin, in the Department ductal carcinoma noted in patient with breast carcinoma.
of Oncology were registered and considered for study. Adenocarcinoma accounts for maximum, about 55.5%,
Patients with less than 15 years of age, with prior history Squamous cell carcinoma, about 35.18%, invasive ductal
of ear disease, ear surgery, noise exposure, trauma, carcinoma about 1.85% and around 7.4% accounting for
suffering with chronic diseases such as diabetes/ other tumours.
hypertension and undergoing chemotherapy with other
platinum group of drugs were excluded from study. Table 1: Incidence of various types of cancer in the
Patients with prior severe to profound sensori-neural study.
hearing loss were not considered as study population.
Patients were selected, admitted in Department of Sl. No. of
Types of cancer %
Oncology, evaluated with necessary investigations No. patients
including complete haemogram, liver and renal function 1. Head and neck carcinoma 13 24.07
tests to undergo chemotherapy. Once the patient has 2. Lung carcinoma 13 24.07
become fit for chemotherapy, patients were further 3. Stomach carcinoma 11 20.37
evaluated in Department of ENT, with relevant history 4. Ovarian carcinoma 2 3.70
taking, meticulous examination of ear is done, prior 5. Oesophageal carcinoma 2 3.70
audiogram is taken before starting the first cycle of Carcinoma breast 1 1.85
6.
chemotherapy and patients were sent back to Oncology
7. Non hodgkins lymphoma 2 3.70
Department for starting chemotherapy.
8. Neuro-ectodermal tumour 1 1.85
Serial audiograms are taken at the end of each cycle up to 9. Malignant Brenner tumour 1 1.85
6 cycles of chemotherapy. Follow-up audiograms are 10. Carcinoma cervix 4 7.40
taken at 3 months and 6 months after completion of 11. Pancreatic carcinoma 4 7.40
chemotherapy. Among 67 patients, 6 patients were Total 54
defaulters for further treatment and 7 patients died during
the course of treatment. Among 54 patients, head and Among 67 registered patients, 6 patients were defaulters
neck carcinoma patients were treated with the dose of 40- for further treatment and 7 patients died during the course
60 mg/sqm, lung, stomach and neuroectodermal of treatment. Among 54 patients under study, 20 patients
carcinoma patients were treated with 60 mg/sqm, ovarian, had normal hearing at the initiation of treatment and 34
nasopharyngeal carcinoma and patients with malignant patients had mild pre-existing hearing loss at the
Brenner tumour were treated with 75 mg/sqm, breast and initiation of treatment. Among 20 patients with normal
pancreatic carcinoma patients were treated with a hearing, 2 patients developed sensorineural hearing loss
maximum of 50 mg/sqm, oesophageal and cervical at the end of treatment and during the follow-up period,
carcinoma patients were treated with 40–60 mg/sqm. All accounting for 5%. Among 34 patients with pre-existing
patients were treated for 3 days with three divided doses. hearing loss, 4 patients had worsened hearing after
treatment. Among 37% of the patients with normal
RESULTS hearing, 10% of the patients developed sensorineural
hearing loss after treatment, accounting for 8.82%.
Among 54 patients, 13 patients had head and neck Among 63% of the patients with prior mild sensorineural
carcinoma, 13 patients had lung carcinoma, 11 patients hearing loss, 11.8% developed worsening of hearing after
had stomach carcinoma, 4 patients had cervical completion of treatment.
carcinoma, 4 patients had periampullary carcinoma, 2
patients had ovarian carcinoma, 2 had oesophageal DISCUSSION
carcinoma, one patient had breast carcinoma, 2 patients
had non-hodgkins lymphoma, one patient had Neuro- Numerous antineoplastic medications are known to be
ectodermal tumour and one had malignant Brenner potentially ototoxic. Cisplatin has been the most
tumour (Table 1). Among 13 patients with head and neck thoroughly studied of the chemotherapeutic agents and is
carcinoma, 6 patients had carcinoma in oral cavity, 2 commonly included in multiple drug treatment protocol.
patients had carcinoma in oropharynx, one patient had The mechanism of cochlear injury in cisplatin
carcinoma of nasopharynx and laryngopharynx each and chemotherapy is by generation of reactive oxygen species

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 Sivasankari L et al. Int J Otorhinolaryngol Head Neck Surg. 2018 Sep;4(5):1297-1300

in all three subregions of organ of corti: stria vascularis, later, total recovery for one patient, but continued
spiral ligament and spiral ganglionic cells. This reactive deterioration for another patient.8 Fausti et al reported on
oxygen species overload leads to the depletion of one patient whose audiogram indicated further
cochlear anti-oxidant enzyme system (e.g. superoxide deterioration of hearing across the frequency range
dismutase– SOD, catalase– CAT, glutathione during follow-up test 5 weeks post-treatment.9 Shulman
peroxidase– GSH-Px and glutathione reductase– GSH-R, et al recommended to assess the cochlear and vestibular
that scavenge and neutralize the superoxides generated. function before, during and at the completion of parental
Thus incease in reactive oxygen species (ROS) drug treatment whenever possible.10 Sweetow et al in
generation leads to increase in proinflammatory their study demonstrated the changes in auditory function
cytokines- leding to inflammation, superoxide formation- following completion of chemotherapy. Schell et al
eventually forming peroxinitryls and 4-hydroxynoenol prospectively tested a large group of patients who
(4HNE) and activation and cleavage of pro-apoptotic received either cisplatin, cranial irradiation or both. They
enzymes such as caspases.3 reported that there was significantly greater potentiation
of ototoxicity, when both therapies done together, but
hearing acquity was either not affected or minimally
affected for irradiation only group.11

Few studies have found the relationship between free

circulating cisplatin in plasma with time. They found that
cisplatin infusion during afternoon and evening results in
low plasma levels of free cisplatin, and hence fewer side
effects including ototoxicity. Measurement of correlation
between time and plasma concentration is beyond the
scope of this study.

The risk of permenant hearing damage from platinum

chemotherapy drugs has stimulated the development of
otoprotectants for co-administration to reduce the hearing
damage without affecting the anti-tumour activity. There
Figure 1: Mechanism of cisplatin. are numerous otoprotectant agents under research,
includes aspirin, antioxidants, intratympanic
The reported hearing loss with cisplatin therapy ranges dexamethasone, hyperbaric oxygen, ginko biloba extract,
from as high as 91% to as low as 9%.4 The potential for diethyldithio carbamate, lipoic acid, vitamin E and
ototoxicity increases with bolus administration and may sodium thiosulphate.12
be reduced by low infusion a long time period. Dose
limitation of cisplatin is usually based on renal CONCLUSION
impairment. Cumulative dose exceeding 400 mg,
concomitant use with other ototoxic medications, Among 37% of the patients with normal hearing, 10% of
previous sensorineural hearing loss and renal dysfunction the patients developed sensorineural hearing loss after
appear to be predisposing factors increasing the treatment. Among 63% of the patients with prior mild
possibility of hearing loss.5 Young patients tend to be sensorineural hearing loss, 11.8% developed worsening
more susceptible to audiological changes associated with of hearing after completion of treatment. Hence,
cisplatin.6 audiologic monitoring is important in patients undergoing
cisplatin chemotherapy and post- chemotherapy auditory
Common symptoms associated with cisplatin ototoxicity monitoring is essential to rehabilitate the patients with
include hearing loss (usually symmetrical but not Sensorineural hearing loss. Auditory rehabilitation with
always), tinnitus (ranging from transient to permanent), hearing aid, ensures the patient to lead a meaningful and
loudness recruitment and otalgia. Ocassionally vestibular improves the quality of life.
symptoms are also reported. Hearing loss initially occurs
in high frequencies and may then progress to low Funding: No funding sources
frequencies, thus affecting intelligibility. Hearing loss Conflict of interest: None declared
may begin shortly after initiation of cisplatin therapy, or Ethical approval: The study was approved by the
initially appear several days after treatment. Tange et al Institutional Ethics Committee
reported that 8 of the 23 cisplatin treated patients,
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