Objectives: To analyze the role of audiometry in considering change to a less ototoxic treatment in head and neck cancer (HNC) patients. Methods: Consecutive patients prescribed high-dose cisplatin (100 mg/m2) between January 2013 and February 2015 were enrolled. Audiometry was performed at baseline and before cisplatin. Change to a less ototoxic agent or reduced cisplatin dose was considered with audiometric decreases >25 dB. Results: A total of 103 patients were included; the median age of the patients was 59 years (range 18−75). Cisplatin was intended curative (58%), adjuvant (32%), or palliative (10%). Forty-two participants (41%) did not commence high-dose cisplatin because of baseline audiometric alterations. Of 61 patients treated with high-dose cisplatin, 40 (66%) showed marked ototoxicity at the end of treatment. The mean hearing loss between initial and final audiometries showed a hearing loss at 4 and 8 kHz in both ears (p = 0.002). Thirteen patients switched to carboplatin and 15 to a lower dose of cisplatin. The outcome was not significantly altered when cisplatin was replaced with carboplatin or cetuximab. Conclusions: Audiometric alterations are common in HNC with high-dose cisplatin, and switching to a less ototoxic regimen does not adversely affect outcome. Audiometric examination could help to prevent hearing loss in this population.

1.
Chan AT, Gregoire V, Lefebvre JL, Licitra L, Hui EP, Leung SF, Felip E; EHNS-ESMO-ESTRO Guidelines Working Group: Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 (suppl 7):vii83-vii85.
2.
Gregoire V, Lefebvre JL, Licitra L, Felip E; EHNS-ESMO-ESTRO Guidelines Working Group: Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(suppl 5):v184-v186.
3.
Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS: Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31:845-852.
4.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL: Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357:1695-1704.
5.
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-1952.
6.
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-1127.
7.
Malhotra H: Cisplatin ototoxicity. Indian J Cancer 2009;46:262-263.
8.
Nitz A, Kontopantelis E, Bielack S, Koscielniak E, Klingebiel T, Langer T, Paulides M: Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients. Oncol Lett 2013;5:311-315.
9.
Paken J, Govender CD, Pillay M, Sewram V: Cisplatin-associated ototoxicity: a review for the health professional. J Toxicol 2016;2016:1809394.
10.
Rademaker-Lakhai JM, Crul M, Zuur L, Baas P, Beijnen JH, Simis YJ, van Zandwijk N, Schellens JH: Relationship between cisplatin administration and the development of ototoxicity. J Clin Oncol 2006;24:918-924.
11.
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK: Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11:21-28.
12.
Chen WC, Jackson A, Budnick AS, Pfister DG, Kraus DH, Hunt MA, Stambuk H, Levegrun S, Wolden SL: Sensorineural hearing loss in combined modality treatment of nasopharyngeal carcinoma. Cancer 2006;106:820-829.
13.
Theunissen EA, Zuur CL, Jozwiak K, Lopez-Yurda M, Hauptmann M, Rasch CR, van der Baan S, de Boer JP, Dreschler WA, Balm AJ: Prediction of hearing loss due to cisplatin chemoradiotherapy. JAMA Otolaryngol Head Neck Surg 2015;141:810-815.
14.
Zuur CL, Simis YJ, Lansdaal PE, Hart AA, Schornagel JH, Dreschler WA, Rasch CR, Balm AJ: Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer. J Clin Oncol 2007;25:3759-3765.
15.
National Cancer Institute: Guidelines for Reporting of Adverse Drug Reactions. Bethesda, National Cancer Institute, Division of Cancer Treatment, 1988.
16.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247.
17.
Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI: Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705-1715.
18.
Landier W, Knight K, Wong FL, Lee J, Thomas O, Kim H, Kreissman SG, Schmidt ML, Chen L, London WB, Gurney JG, Bhatia S: Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales - a report from the Children's Oncology Group. J Clin Oncol 2014;32:527-534.
19.
Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, Branchereau S, Aronson D, Rangaswami A, Ronghe M, Casanova M, Sullivan M, Morland B, Czauderna P, Perilongo G: Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol 2013;14:834-842.
20.
Hamauchi S, Yokota T, Onozawa Y, Ogawa H, Onoe T, Kamijo T, Iida Y, Nishimura T, Onitsuka T, Yasui H: Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin. Jpn J Clin Oncol 2015;45:1116-1121.
21.
Marshak T, Steiner M, Kaminer M, Levy L, Shupak A: Prevention of cisplatin-induced hearing loss by intratympanic dexamethasone: a randomized controlled study. Otolaryngol Head Neck Surg 2014;150:983-990.
22.
Riga MG, Chelis L, Kakolyris S, Papadopoulos S, Stathakidou S, Chamalidou E, Xenidis N, Amarantidis K, Dimopoulos P, Danielides V: Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: a feasible method with promising efficacy. Am J Clin Oncol 2013;36:1-6.
23.
Fouladi M, Chintagumpala M, Ashley D, Kellie S, Gururangan S, Hassall T, Gronewold L, Stewart CF, Wallace D, Broniscer A, Hale GA, Kasow KA, Merchant TE, Morris B, Krasin M, Kun LE, Boyett JM, Gajjar A: Amifostine protects against cisplatin-induced ototoxicity in children with average-risk medulloblastoma. J Clin Oncol 2008;26:3749-3755.
24.
van As JW, van den Berg H, van Dalen EC: Medical interventions for the prevention of platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev 2012;5:CD009219.
25.
Grau JJ, Estape J, Cuchi MA, Firvida JL, Blanch JL, Ascaso C: Calcium supplementation and ototoxicity in patients receiving cisplatin. Br J Clin Pharmacol 1996;42:233-235.
26.
Chang J, Ryou N, Jun HJ, Hwang SY, Song JJ, Chae SW: Effect of cigarette smoking and passive smoking on hearing impairment: data from a population-based study. PLoS One 2016;11:e0146608.
27.
Itoh A, Nakashima T, Arao H, Wakai K, Tamakoshi A, Kawamura T, Ohno Y: Smoking and drinking habits as risk factors for hearing loss in the elderly: epidemiological study of subjects undergoing routine health checks in Aichi, Japan. Public Health 2001;115:192-196.
28.
Kim JS: Prevalence and factors associated with hearing loss and hearing aid use in Korean elders. Iran J Public Health 2015;44:308-317.
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