CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2022; 43(05): 424-430
DOI: 10.1055/s-0042-1755546
Original Research Article

Prospective Observational Study of Evaluating Cisplatin-Induced Ototoxicity in Patients

Pooja D. Halani
1   Department of Medical Oncology, Apollo CBCC Cancer Care, Ahmadabad, Gujarat, India
,
Rajdeep J. Gupta
1   Department of Medical Oncology, Apollo CBCC Cancer Care, Ahmadabad, Gujarat, India
,
Akash M. Shah
1   Department of Medical Oncology, Apollo CBCC Cancer Care, Ahmadabad, Gujarat, India
,
Shirish S. Alurkar
1   Department of Medical Oncology, Apollo CBCC Cancer Care, Ahmadabad, Gujarat, India
› Author Affiliations
FundingPure-tone audiometry charges were taken care by primary investigator and from hospital research fund.

Abstract

Introduction Platinum-based chemotherapeutic agents cisplatin and carboplatin are two of the most widely used drugs in cancer today. They display wide range of adverse reactions; among them, ototoxicity is an important cumulative toxicity that more commonly observed with cisplatin. At a later stage, it can affect speech of individual and lead to communication problem with decreased cognitive function and depression in cancer survivors. Periodic monitoring of hearing loss with pure-tone audiometry (PTA) provides early evidence of ototoxicity which may decrease debilitating effect of the same in a patient.

Objective The primary objective of this study was to assess cisplatin-induced ototoxicity. We also investigated its severity, reversibility, and other modifying risk factors.

Materials and Methods We conducted a prospective observational descriptive type of epidemiological study. The study was conducted over 80 randomly selected cancer patients (for estimation of sample size, the following formula was used n = [ 2 PQ] / d 2), who were starting with their first cycle of cisplatin from August 2018 to July 2020. This study was conducted at tertiary cancer care center in western Gujarat which caters patients from all over India. We performed PTA in all randomized patients at baseline and periodically. We classified hearing loss according to the World Health Organization (WHO) criteria.

Results A total of 30% (n = 24) patients developed cisplatin-induced ototoxicity according to WHO criteria at end of 3 months after starting the first cycle of cisplatin. It was sensory neuronal, affecting both the ears equally, and was seen predominantly at high frequency. We observed hearing loss at 3 months to be significantly more common in the 301 to 400 mg/m2 cumulative dose group (47%), as compared with the other two groups (0–200 mg/m2 and 201–300 mg/m2; p < 0.05). It showed dose dependency with cisplatin. In the multivariate step-wise regression model, baseline hearing loss (odds ratio [OR] = 17.71, 95% confidence interval [CI]: 6.57–118.91, p < 0.05) and cumulative cisplatin dose of more than 300 mg/m2 were significantly associated with hearing loss at 3 months (OR = 6.62, 95% CI: 2.33–18.74, p < 0.05).

Conclusion Cisplatin-induced ototoxicity manifests as a bilateral high frequency sensorineural hearing loss. Cumulative dose of cisplatin is an important predictor of development of ototoxicity. Baseline and periodic audiometric monitoring could detect ototoxicity early which leads to possible limitation on the severity of ototoxicity.



Publication History

Article published online:
20 October 2022

© 2022. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Sung H, Ferlay J, Siegel RL. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71 (03) 209-249
  • 2 Simon T, Hero B, Dupuis W, Selle B, Berthold F. The incidence of hearing impairment after successful treatment of neuroblastoma. Klin Padiatr 2002; 214 (04) 149-152
  • 3 Rademaker-Lakhai JM, Crul M, Zuur L. et al. Relationship between cisplatin administration and the development of ototoxicity. J Clin Oncol 2006; 24 (06) 918-924
  • 4 Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; Pharmaceutical Society of Australia; Royal Australian College of General Practitioners. Australian Medicines Handbook. Adelaide, Australia: Pharmeutical Society of Australia; 2017
  • 5 Landier W. Ototoxicity and cancer therapy. Cancer 2016; 122 (11) 1647-1658
  • 6 Oldenburg J, Kraggerud SM, Cvancarova M, Lothe RA, Fossa SD. Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors. J Clin Oncol 2007; 25 (06) 708-714
  • 7 Riedemann L, Lanvers C, Deuster D. et al. Megalin genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Pharmacogenomics J 2008; 8 (01) 23-28
  • 8 Brock PR, Maibach R, Childs M. et al. Sodium thiosulfate for protection from cisplatin-induced hearing loss. N Engl J Med 2018; 378 (25) 2376-2385
  • 9 Konrad-Martin D, Helt WJ, Reavis KM. et al. Ototoxicity: early detection and monitoring. ASHA Lead 2005; 10: 1-4
  • 10 Parsa V, Scollie S, Glista D, Seelisch A. Nonlinear frequency compression: effects on sound quality ratings of speech and music. Trends Amplif 2013; 17 (01) 54-68
  • 11 Durrant JD, Campbell K, Fausti S. et al. American Academy of Audiology: position statement and clinical practice guidelines: ototoxicity monitoring. Accessed July 26, 2022 at: https://audiology-web.s3.amazonaws.com/migrated/OtoMonGuidelines.pdf_539974c40999c1.58842217.pdf
  • 12 American Speech-Language-Hearing Association. Audiologic management of individuals receiving cochleotoxic drug therapy (guideline). Accessed July 26, 2022 at: https://www.asha.org/policy/gl1994-00003/
  • 13 American Speech-Language-Hearing Association. Audiologic management of individuals receiving cochleotoxic drug therapy. ASHA 1994; 36: 1-19
  • 14 World Health Organization. Report of the informal working group on prevention of deafness and hearing impairment programme planning. Accessed July 26, 2022 at: https://apps.who.int/iris/bitstream/handle/10665/58839/WHO_PDH_91.1.pdf?sequence=1&isAllowed=y
  • 15 Arslan E, Orzan E, Santarelli R. Global problem of drug-induced hearing loss. Ann N Y Acad Sci 1999; 884: 1-14
  • 16 Wang J, Lloyd Faulconbridge RV, Fetoni A, Guitton MJ, Pujol R, Puel JL. Local application of sodium thiosulfate prevents cisplatin-induced hearing loss in the guinea pig. Neuropharmacology 2003; 45 (03) 380-393
  • 17 Macdonald MR, Harrison RV, Wake M, Bliss B, Macdonald RE. Ototoxicity of carboplatin: comparing animal and clinical models at the Hospital for Sick Children. J Otolaryngol 1994; 23 (03) 151-159
  • 18 Gonçalves MS, Silveira AF, Teixeira AR, Hyppolito MA. Mechanisms of cisplatin ototoxicity: theoretical review. J Laryngol Otol 2013; 127 (06) 536-541
  • 19 Hellberg V, Wallin I, Ehrsson H, Laurell G. Cochlear pharmacokinetics of cisplatin: an in vivo study in the guinea pig. Laryngoscope 2013; 123 (12) 3172-3177
  • 20 Olgun Y. Cisplatin ototoxicity: where we are?. J Int Adv Otol 2013;9(03):
  • 21 Wang J, Puel JL, Bobbin R, Bobbin R, Puel JL. Mechanisms of toxicity in the cochlea (including physical free radical: oxidative and anti-oxidative mechanisms, protein interactions, and defense mechanisms). In: Campbell KC. Pharmacology and Ototoxicity for Audiologists. Clifton Park, NY: Delmar Cengage Learning; 2007: 70-81
  • 22 Dwivedi G, Kumar M, Gupta V, Sood A, Patnaik U. A clinical study of cisplatin induced ototoxicity in head and neck malignancies. Int J Otorhinolaryngol Head Neck Surg 2019; 5: 1044-1051
  • 23 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 (04) 311-317
  • 24 Dutta A, Venkatesh MD, Kashyap RC. Study of the effects of chemotherapy on auditory function. Indian J Otolaryngol Head Neck Surg 2005; 57 (03) 226-228
  • 25 Greene JB, Standring R, Siddiqui F, Ahsan SF. Incidence of cisplatin induced ototoxicity in adults with head and neck cancer. Advances in Otolaryngology 2015; 2015: 245613
  • 26 Bokemeyer C, Berger CC, Hartmann JT. et al. Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Br J Cancer 1998; 77 (08) 1355-1362
  • 27 Frisina RD, Wheeler HE, Fossa SD. et al. Comprehensive audiometric analysis of hearing impairment and tinnitus after cisplatin-based chemotherapy in survivors of adult-onset cancer. J Clin Oncol 2016; 34 (23) 2712-2720
  • 28 Cho SI, Lee JE, Do NY. Protective effect of silymarin against cisplatin-induced ototoxicity. Int J Pediatr Otorhinolaryngol 2014; 78 (03) 474-478
  • 29 Whitehorn H, Sibanda M, Lacerda M. et al. High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa. S Afr Med J 2014; 104 (04) 288-291
  • 30 Skalleberg J, Solheim O, Fosså SD. et al. Long-term ototoxicity in women after cisplatin treatment for ovarian germ cell cancer. Gynecol Oncol 2017; 145 (01) 148-153
  • 31 Helson L, Okonkwo E, Anton L, Cvitkovic E. cis-Platinum ototoxicity. Clin Toxicol 1978; 13 (04) 469-478
  • 32 Yancey A, Harris MS, Egbelakin A, Gilbert J, Pisoni DB, Renbarger J. Risk factors for cisplatin-associated ototoxicity in pediatric oncology patients. Pediatr Blood Cancer 2012; 59 (01) 144-148
  • 33 Jacob LC, Aguiar FP, Tomiasi AA, Tschoeke SN, Bitencourt RF. Auditory monitoring in ototoxicity. Rev Bras Otorrinolaringol (Engl Ed) 2006; 72 (06) 836-844
  • 34 Yu KK, Choi CH, An YH. et al. Comparison of the effectiveness of monitoring Cisplatin-induced ototoxicity with extended high-frequency pure-tone audiometry or distortion-product otoacoustic emission. Korean J Audiol 2014; 18 (02) 58-68