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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 21  |  Issue : 4  |  Page : 243-247

Auditory alterations following chemoradiotherapy: A comparative study between cisplatin and paclitaxel


1 Department of ENT, SMGS Hospital, GMC, Jammu, Jammu and Kashmir, India
2 Department of ENT, KGMU, Lucknow, Uttar Pradesh, India
3 Department of ENT, Jain ENT Hospital, Jaipur, Rajasthan, India

Date of Web Publication16-Oct-2015

Correspondence Address:
Rohan Gupta
Jain ENT Hospital, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-7749.167411

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  Abstract 

Aim: To study the auditory effects of chemoradiotherapy with cisplatin and paclitaxel. Materials and Methods: Eighty patients with head and neck cancer undergoing chemoradiotherapy with cisplatin or paclitaxel were enrolled for the present study and monitored for any auditory alterations. Results: Forty-eight patients underwent chemotherapy with cisplatinum while 32 patients with paclitaxel. Hearing loss was observed along with tinnitus, vertigo, and nausea and vomiting. Conclusion: Taxanes-based chemoradiotherapy cause less auditory alterations than cisplatin-based chemoradiotherapy.

Keywords: Auditory alteration, Chemotherapy, Cisplatin, Paclitaxel


How to cite this article:
Kaul A, Gupta N, Gupta R, Singh I P, Kotwal S. Auditory alterations following chemoradiotherapy: A comparative study between cisplatin and paclitaxel. Indian J Otol 2015;21:243-7

How to cite this URL:
Kaul A, Gupta N, Gupta R, Singh I P, Kotwal S. Auditory alterations following chemoradiotherapy: A comparative study between cisplatin and paclitaxel. Indian J Otol [serial online] 2015 [cited 2020 Feb 23];21:243-7. Available from: http://www.indianjotol.org/text.asp?2015/21/4/243/167411


  Introduction Top


Chemotherapy (CT) has been used most frequently in the treatment of head and neck cancers, mainly in association with radiotherapy. One of the most commonly used drug for this purpose is cisplatin. Despite its therapeutic action, there are some known adverse effects, among which ototoxic effects are the most significant. It has been reported in the past that high-dose cisplatin CT schemes induced a 58–81% incidence of hearing loss at frequencies from 0.250 to 8 kHz while other workers have reported an incidence of up to 46%. In addition, radiation-induced sensorineural hearing loss (SNHL) has been observed to have an incidence of 49% immediately after treatment. Studies on combined modality treatment with intravenously applied high-dose cisplatin and radiotherapy, 53% SNHL was more than 30 dB at 4 and 8 kHz and incidence of ototoxicity interfering with CT regimen were described.[1] Nowadays, platinum-based CT concurrent with radiation therapy (XRT) has become widely used in the treatment of head and neck malignancy. This is supported by reporting an improved survival for concurrent therapy compared with RT alone.

Other than cisplatin, taxanes have also been used in concomitant regimen of chemoradiotherapy, in the treatment of advanced head and neck cancers.[2] Combined modality therapy plays a central role in the management of head and neck malignancies. The study of feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel and XRT showed complete response after the paclitaxel, which was given every 3 weeks at a dose of 100 mg/m 2 concurrently with external beam radiation. As expected, significant local toxicity was observed.[3]

The identification of the auditory effects after combined radiochemotherapy may be helpful to guide preventive actions. Thus, the aim of the present study is to note the auditory alterations in patients of advanced head and neck cancer undergoing chemoradiotherapy, and comparing effects of combination of cisplatin and radiotherapy with a combination of taxanes and radiotherapy.


  Materials and Methods Top


The present study was conducted in the Department of ENT, SMGS Hospital, Government Medical College, Jammu, in collaboration with the Department of Radiotherapy, Government Medical College, Jammu for a period of 1 year, that is, from August, 2013 to July, 2014 on 100 patients with histopathologically proven head and neck malignancies, out of which 20 patients were lost on follow-up and finally excluded.

Exclusion criteria

Subjects excluded were those who had:

  • History of hearing or vestibular disturbances previous to the diagnosis of head and neck malignancy
  • Risk of occupational otological disease (external noise exposure)
  • Diabetes or other metabolic diseases
  • Hypertension and other cardiovascular diseases
  • External or middle ear pathologies on clinical examination.


Cases included in the study were the cases with World Health Organization (WHO) performance status of 0 and 1.

Patients attending/admitted in the Department of ENT., with cancer of head and neck, were assessed thoroughly before start, during, and at completion of treatment on the following pattern, that is, history, examination, investigation; and otologic and neuro-otologic assessment.

Pure tone audiometry (PTA) was done, before start of treatment, during mid-treatment, at the end of treatment, and once a month for next 3 months. Hearing loss was classified according to WHO Classification: 0–25 dB not significant, 26–40 dB mild, 41–55 dB moderate, 56–70 dB moderately severe, 71–90 dB severe, and >91 dB profound. However, hearing loss of >10 dB either in speech frequency or high frequency was considered significant.[4]

Neuro-otology examination was also done at the start of treatment and after finishing the treatment, which include Romberg test, cerebellar function test, cranial nerves examination, nystagmus, caloric test, fistula test, rotatory chair test, and Dix–Hallpike.

Impedance audiometry and special tests of hearing (tone decay test, recruitment, short increment sensitivity index, etc.) if required were done during, at start, and at completion of treatment.

Concomitant chemoradiotherapy was given as per standard recommendation procedures. Cisplatin (30 mg/m 2) or pactitaxel (40 mg/m 2), were given in weekly dose along with radical doses of radiotherapy.


  Results Top


The present study is conducted jointly in the Department of ENT and Head and Neck Surgery, SMGS Hospital and Department of Radiotherapy, Government Medical College, Jammu, during which 80 cases of head and neck cancers with no previous hearing loss or vestibular disturbances prior to diagnosis, were enrolled.

All the patients were taken up for thorough examination; and PTA was done at the start, the mid, the end of treatment, and also at monthly follow-up. Patients were followed up for 3 months after completion of treatment.

Out of the 80 patients enrolled for the present study, there were 58 (72.5%) male and 22 (27.5%) female patients. Maximum patients in the study were in age groups 41–50 years and 51–60 years with the mean age being 50.95 ± 8.6 years [Table 1].
Table 1: Distribution of patients according to age and gender

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Out of the 58 male patients, 36 underwent CT with cisplatinum and 22 with paclitaxel. 12 out of the 22 females underwent cisplatinum-based CT while 10 were treated with paclitaxel-based CT [Table 2].
Table 2: Distribution of patients according to gender and treatment modality

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All patients with carcinoma involving PNS and nasopharynx underwent radiotherapy and CT with paclitaxel. Most of the oral cavity and oropharyngeal cancers underwent XRT + CT (cisplatinum) while some underwent XRT + CT (taxanes). Hypopharyngeal carcinoma patients underwent XRT + cisplatinum based CT while laryngeal carcinoma patients underwent XRT + CT (cisplatinum) and XRT + CT (taxanes) in equal numbers [Table 3].
Table 3: Distribution of patients according to treatment modality, sites and subsite of malignancy

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Patients undergoing XRT + CT (cisplatinum) had symptoms of alteration in hearing, tinnitus, nausea and vomiting, ear fullness, and vertigo; while those treated with XRT + CT (taxanes) complained only of aural fullness and alterations in hearing, with nausea and vomiting and vertigo, not being presented by any of the patients [Table 4].
Table 4: Distribution of patients according to symptoms (subjective complaints pertaining to ear) of head--neck malignancies and treatment modality

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All the patients under chemoradiotherapy irrespective of cistplatinum or taxanes showed bilaterality in hearing loss, but it was slightly more with cisplatinum. XRT + CT (taxanes) caused significant hearing loss in 12.5% patients (both ears) in high frequency and in 6.2% patients in speech frequency; whereas with XRT + CT (cisplatinum) the number was slightly more, that is, 8.3% in speech frequencies and 20.8% in high frequency [Table 5].
Table 5: Distribution of patients according to audiometric changes in cases of head-neck malignancies and treatment modality

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Patients of oral cavity and oropharyngeal cancers undergoing XRT + CT (cistplatinum) showed decrease in hearing; however, it was not seen in the patients undergoing XRT + CT (taxanes). Patients with laryngeal carcinoma on XRT + CT (cistplatinum), showed bilateral hearing loss, with four patients developing high frequency hearing loss and two patients developing hearing loss involving both the frequencies. No hearing loss was seen in the six patients of laryngeal carcinoma who underwent XRT + CT (taxanes). All the patients except those with nose, PNS, and nasopharyngeal carcinoma, did not get significant hearing loss in any frequency by XRT + CT (taxanes).

Diagnosis of serous otitis media (SOM) was made by impedance audiometry which showed a change in curve from A to C followed by reversal of C to A with drug therapy. Stapedial reflexes, both ipsilateral and contralateral were present in all the cases. All cases of nasopharyngeal carcinoma developed SOM during treatment. Small group of patients (6), being treated with XRT + CT (taxanes) developed SOM mostly in mid-treatment, whereas no SOM was seen in the group of patients receiving XRT + CT (cistplatinum) [Table 6].
Table 6: SOM in patients of head-neck malignancies

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Progression of SNHL during treatment showed typical characteristic of increase in severity with treatment, reaching maximum by end of treatment, that is, moderate to moderately severe in XRT + CT and declining thereafter to normal hearing by 1-month in all patients. Among both modalities, XRT + CT (cisplatinum) showed maximum hike in hearing loss, which resolved thereafter [Table 7].
Table 7: Change in degree of hearing threshold with duration in progression of SNHL

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  Discussion Top


The current treatment strategies of head and neck malignancies aim not only on the management of tumor but also on organ preservation, because of this radiotherapy along with CT have attained an important role. The present study was therefore conducted on 80 patients with histopathologically proven head and neck malignancies, to study the auditory alteration pattern following chemoradiotherapy, comparing two chemotherapeutic agents, that is, cisplatin and paclitaxel.

In the present study of patients undergoing XRT + CT (cisplatinum), 10 (20.83%) patients reported hearing alteration; 6 (12.50%) patients had tinnitus, aural fullness, and SOM were present in 8 (16.67%) patients each while vertigo and nausea were present in 2 (4.17%) patients each.

Similar study was conducted by Pandey et al.[5] in which hearing impairment and tinnitus was observed in nine and seven patients, respectively while nausea and vomiting were present in significant number of patients (80%). However, there was no case reported of SOM and ear fullness.

In the present study, one case of vertigo following cisplatinum-based radiotherapy revealed vestibulotoxicity of cisplatinum. Same results were observed by Black et al.[6] who in their study of 16 patients, treated with CT (cisplatinum) noticed vestibulotoxicity in 3, but two of these three patients had abnormally low function prior to cisplatinum therapy.

In the present study of patients undergoing XRT + CT (taxanes), ear fullness and SOM was noticed in 12 (37.5%) patients each, 6 (18.75%) patients reported altered hearing, while 2 (6.25%) patients developed tinnitus.

A similar study conducted by Liberman et al.[7] reported 4 out of 11 patients (36%) to have hearing loss after the treatment in larynx; however, it was mild and asymptomatic. A study by Arora et al.[8] observed subjective hearing loss in seven patients while six patients had tinnitus during the CT. The hearing loss was sensorineural, dose-dependent, symmetrical, bilateral, and irreversible. Higher frequencies were first to be affected in cisplatin CT.

The patients receiving RT with taxanes experienced less hearing loss as compared to patients receiving XRT + CT (cisplatinum), in the present study. This is in accordance with the study of Pandey et al.[5] who observed significant hearing loss with XRT + cistplatinum while they did not give taxanes to their patients.

As far as auditory alteration is considered, the present study had slightly less percentage of patients as compared to the study of Liberman et al.[7] who had 36% patients with hearing loss following XRT + CT. It could be due to use of both cisplatin and paxlitaxel drugs for CT on patients. No study was found in literature to report SOM, tinnitus, and ear fullness following XRT + CT (taxanes).

In a study done by Dell'Aringa et al.[9] on 17 patients with head and neck cancers treated by CT using cisplatin and radiotherapy it was found that 70.5% left ears and 64.7% right ears presented decrease in hearing soon after treatment for frequency 1 kHz (mid auditory damage) and for the frequency 8 kHz (more significant auditory damage).

In the present study, all the patients of hearing loss had SNHL barring; few patients who developed mixed hearing loss had (both SNHL and conductive hearing loss [CHL]) during treatment. However, CHL resolved by the 1st month following completion of treatment. CHL was mainly due to SOM which developed in cases of nasopharynx and carcinoma buccal mucosa undergoing treatment by XRT + CT (taxanes); however, no patient of XRT + CT (cisplatinum) had developed CHL during treatment.

Diagnosis of SOM was made by impedance audiometry which showed change in curve for A to C followed by reversal of C curve to A. These findings in the present study are consistent with the study by Pandey et al.[5] which reported a change in curve from A to C in seven cases followed by change from C to A in four cases and A to As in three cases and C to B in one case.

In XRT + CT groups, more than 10 dB hearing loss was seen in all the frequencies, viz. speech, high and both, with bilaterality of the ears involved, probably due to general effect of CT. Hearing loss occurred in high frequencies in 10 (20.8%) patients receiving cisplatinum with XRT, while only 4 (8.3%) patients had hearing loss in both speech and high frequencies. Similarly, with XRT + CT (taxanes), 12.5% and 6.2% of patients were seen with hearing loss in high frequency and in both (speech and high) frequencies, respectively. All these observations are in consonance with those reported by Pandey et al.[5]

The present study is consistent with that conducted by Pearson et al.[10] who carried a study on 37 patients undergoing XRT + CT (cisplatinum) and found that more than 50% of patients had a change of 10 dB or greater following XRT + CT (cisplatinum). More than 85% patients experienced changes in their hearing at 4 and 8 kHz. Zuur et al.[1] also revealed that XRT + CT (cisplatinum) induced SNHL in their study with short-term follow-up.


  Conclusion Top


XRT + CT (taxanes) are less toxic to the otologic structures as compared to the cisplatinum-based radiochemotherapy. No vestibulotoxicity could be noticed by XRT + CT (taxanes).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Zuur CL, Simis YJ, Lansdaal PE, Hart AA, Rasch CR, Schornagel JH, et al. Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: A multivariate analysis. Int J Radiat Oncol Biol Phys 2007;68:1320-5.  Back to cited text no. 1
    
2.
Adelstein DJ, Leblanc M. Does induction chemotherapy have a role in the management of locoregionally advanced squamous cell head and neck cancer? J Clin Oncol 2006;24:2624-8.  Back to cited text no. 2
    
3.
Tishler RB, Busse PM, Norris CM Jr, Rossi R, Poulin M, Thornhill L, et al. An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies. Int J Radiat Oncol Biol Phys 1999;43:1001-8.  Back to cited text no. 3
    
4.
Schot LJ, Hilgers FJ, Keus RB, Schouwenburg PF, Dreschler WA. Late effects of radiotherapy on hearing. Eur Arch Otorhinolaryngol 1992;249:305-8.  Back to cited text no. 4
    
5.
Pandey A, Raizada RM, Puttewar MP, Singh AKK, Baitha S, Chaturvedi VN. Effects of radiation therapy and Chemotherapy on otological structures in head, neck and oesophageal malignancies. Indian J Otolartngol Head Neck Surg 2005;Special issue 1:33-9.  Back to cited text no. 5
    
6.
Black FO, Myers EN, Schramm VL, Johnson J, Sigler B, Thearle PB, et al. Cisplatin vestibular ototoxicity: Preliminary report. Laryngoscope 1982;92:1363-8.  Back to cited text no. 6
    
7.
Liberman PH, Schultz C, Gomez MV, Carvalho AL, Pellizzon AC, Testa JR, et al. Auditory effects after organ preservation protocol for laryngeal/hypopharyngeal carcinomas. Arch Otolaryngol Head Neck Surg 2004;130:1265-8.  Back to cited text no. 7
    
8.
Arora R, Thakur JS, Azad RK, Mohindroo NK, Sharma DR, Seam RK. Cisplatin-based chemotherapy: Add high-frequency audiometry in the regimen. Indian J Cancer 2009;46:311-7.  Back to cited text no. 8
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9.
Dell'Aringa AH, Isaac ML, Arruda GV, Esteves MC, Dell'aringa AR, Júnior JL, et al. Audiological findings in patients treated with radio- and concomitant chemotherapy for head and neck tumors. Radiat Oncol 2009;4:53.  Back to cited text no. 9
    
10.
Pearson SE, Meyer AC, Adams GL, Ondrey FG. Decreased hearing after combined modality therapy for head and neck cancer. Am J Otolaryngol 2006;27:76-80.  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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