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Revista CEFAC

Print version ISSN 1516-1846On-line version ISSN 1982-0216

Rev. CEFAC vol.22 no.2 São Paulo  2020  Epub Feb 17, 2020 


Effects of chemotherapy on the auditory system of children with cancer: a systematic literature review

Nila Bernardes Lopes1

Liliane Aparecida Fagundes Silva1

Alessandra Giannella Samelli1

Carla Gentile Matas1

1 Universidade de São Paulo, Faculdade de Medicina - FMUSP, Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional, São Paulo, São Paulo, Brasil.



to identify and analyze the effects of chemotherapy on the auditory system of children and/or adolescents with cancer treated with cisplatin and carboplatin, assessed through standardized audiological procedures.


studies in Brazilian Portuguese and in English were searched for, as available in the databases Science Direct, PubMed, LILACS, BIREME, Embase, SciELO, Web of Science and Cochrane. The descriptors were: Hearing Loss, Audiology, Child Cancer, Chemotherapy, and Child. Articles with levels 1 and 2 of scientific evidence, published in the last 20 years (1997 to 2017), were considered, of which the audiological results were analyzed, as well as the prevalence of hearing loss in children with cancer undergoing chemotherapy.


3,625 articles were found, of which only 23 were selected for analysis in the present review. Studies have shown a high incidence of sensorineural hearing loss and decrease or even loss of otoacoustic emissions in children and adolescents with cancer, even after the first dose of chemotherapy drugs, with high frequencies being the most affected.


there is evidence that both carboplatin and especially cisplatin from the first doses may impair the hearing of children and adolescents, mainly affecting the cochlear function, thus, the importance of long-term audiological monitoring.

Keywords: Hearing Loss; Cancer; Child; Chemotherapy; Audiology



identificar e analisar os efeitos da quimioterapia no sistema auditivo de crianças e/ou adolescentes com câncer tratados com cisplatina e carboplatina, avaliados por meio de procedimentos audiológicos padronizados.


buscou-se por estudos nos idiomas português brasileiro e inglês, disponíveis nas bases de dados Science Direct, PubMed, Lilacs, Bireme, Embase, Scielo, Web of Science e Cochrane. Os descritores foram: Perda Auditiva, Audiologia, Câncer Infantil, Quimioterapia e Criança. Foram considerados artigos com níveis de evidência científica 1 e 2, publicados nos últimos 20 anos (1997 a 2017), dos quais foram analisados os resultados audiológicos, bem como a prevalência da perda auditiva de crianças com câncer submetidas à quimioterapia.


foram encontrados 3625 artigos, sendo que apenas 23 foram selecionados para análise na presente revisão. Os estudos demonstraram alta incidência de perda auditiva neurossensorial e diminuição ou até perda das emissões otoacústicas em crianças e adolescentes com câncer, mesmo após a primeira dose das drogas quimioterápicas, sendo que as frequências altas são as mais acometidas.


há evidências de que a carboplatina e especialmente a cisplatina, desde as primeiras doses, podem prejudicar a audição de crianças e adolescentes, afetando principalmente a função coclear, destacando a importância do monitoramento audiológico a longo prazo.

Descritores: Perda Auditiva; Câncer; Criança; Quimioterapia; Audiologia


Child and adolescent cancer (involving children and adolescents between zero and 19 years old) is a disease with characteristics of its own, especially concerning histopathology and clinical behavior. In general, child and adolescent cancer presents short latency periods, grows faster, and is more aggressive. However, it responds better to treatment and has good prognosis1.

Chemotherapy is a mode of systemically treating the oncologic patient, more recent than surgery and radiotherapy, and it consists in administrating chemical substances, either alone or in combination, with the objective of destroying malignant neoplastic cells, while preserving the normal ones2.

The antineoplastic therapy includes the use of various drugs, among which are the alkylating agents, which are chemical substances capable of replacing a hydrogen atom by an alkyl radical. Platinum compounds, including cisplatin, carboplatin and oxaliplatin, can penetrate the cells by diffusion and modifying the DNA molecules, which are indispensable for the cell replication process3.

Among the many collateral effects resulting from chemotherapy, ototoxicity is one that may cause lesions to the inner ear structures, resulting in hearing loss, normally, sensorineural, bilateral and symmetric, affecting first the higher frequencies4,5. Producing free radicals with the use of antineoplastic therapeutic agents may change the cell wall and the cells’ genetic material, including the cochlea’s hair cells. Thus, basic mechanisms of these collateral effects involve the production of reactive oxygen species in the cochlea that induce these cells to death, making it impossible for the electrical signals to be adequately transmitted to the auditory nerve6.

It is known that platinum compound-induced hearing loss may vary from zero to 90.1%7. Furthermore, some studies have described that hearing loss may be triggered during the platinum-based therapy, or even develop after the treatment has finished5,8,9.

Moreover, in the literature there are studies relating possible factors that contribute to the seriousness of the hearing loss. For instance, higher cisplatin dosages, as well as younger patients, can maximize the ototoxic effects of the platinum compound10,11. On the other hand, it is shown that even individual dosages can impair the auditory system12.

Although cisplatin ototoxicity has been carefully investigated, much less is known about ototoxicity caused by carboplatin. Factors that can potentialize carboplatin ototoxicity are known to include previous exposure to cisplatin or other ototoxic medications, or high carboplatin dosages13.

Carboplatin, which is considered less ototoxic than cisplatin, proved to be highly toxic for the cochlea’s inner hair cells and type I ganglion neurons in animals14. Conversely, another study observed that ototoxic complications from carboplatin chemotherapy were rarer and mild15.

A systematic review recently published described varied prevalence of hearing loss induced by platinum compounds (cisplatin, carboplatin or both, in different doses). However, this review focused on the description of the findings related to the prevalence of hearing loss and to symptomatology resulting from the effects of ototoxicity7.

Considering that there are still gaps on the knowledge about the effects of platinum compounds on the auditory pathway, it is important that studies describing the results of audiological procedures on the subject be developed, to investigate on what part of the auditory system there is more impact of the platinum agents. Thus, it would be possible to offer better guidance on the need and the form of auditory monitoring in this population. It is known that such monitoring is extremely important to detect possible auditory alterations in due time and, whenever possible, reconsider treatment possibilities4,9.

Hence, this study aimed at identifying and analyzing the effects of chemotherapy on the auditory system of children and/or adolescents with cancer, treated with cisplatin and carboplatin, assessed through standardized audiological procedures.


Research Strategy

Initially, the following research question was developed and defined: What are the effects of carboplatin and cisplatin treatment on the auditory system of children and adolescents with cancer, assessed through standardized audiological procedures?

The systematic review was conducted in compliance with the recommendations by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)16. Within the PRISMA strategy, the PICO (population, intervention, comparison/control, outcome)17 was used to formulate the objective of the study:

  • Patient (P): children or adolescents with cancer undergoing chemotherapy carboplatin and/or cisplatin treatment;

  • Intervention (I): containing audiological assessment data (acoustic immittance, pure-tone audiometry, otoacoustic emissions - OAE - and/or brainstem auditory evoked potentials - BAEP) of individuals undergoing carboplatin and/or cisplatin chemotherapy treatment;

  • Comparison (C): the comparison of longitudinal results (before and after chemotherapy) was considered, as well as the comparison with criteria of normality defined in the literature;

  • Outcomes (O): either presenting or not audiological alterations, considering type, degree, configuration and/or prevalence of hearing loss.

The search was conducted on the electronic databases MEDLINE-PubMed, Science Direct, LILACS, Embase, SciELO, Web of Science and Cochrane, with the following descriptors: Hearing Loss, Audiology, Childhood Cancer, Chemotherapy, Drug Therapy, Child. The descriptors were used in English, in accordance with the Medical Subject Headings (MeSH), and in Portuguese, in accordance with the Health Sciences Descriptors (DeCS, its Portuguese acronym). These descriptors were combined with the Boolean operator “AND”.

Selection Criteria

The period selected for inclusion of studies in Portuguese or English was the last 20 years (1997 to 2017). The ones included, in general, were original articles dealing with the hearing of children and adolescents with cancer submitted to cisplatin and/or carboplatin chemotherapy treatment, with levels 1 and 2 of scientific evidence according to the Oxford Centre for Evidence-based Medicine18. These articles included: systematic review of randomized controlled clinical trials or of cohort studies, randomized controlled clinical trial with narrow confidence interval, “all or nothing” therapeutic results, cohort studies and therapeutic results observation. Articles with expert opinion, case reports, case-control studies and systematic literature reviews were excluded, as well as studies including the use of otoprotective agents.

The selection of the articles was carried out by two researchers. At first, the articles obtained through the search on the databases were identified; then, the articles were selected, excluding the duplicated ones and those not related to the defined descriptors, through the screening of titles and summaries; after this step, the eligibility was conducted with the full reading of the texts, excluding the articles not meeting the previously established criteria; lastly, the eligible articles were included in the systematic review.

Data Analysis

After finishing the collection from the databases, a table was filled out with the data from each study in order to exclude repeated articles. Two independent researchers conducted the analysis of the texts found, selecting the texts that met the inclusion criteria. For an initial filtering, the title of each article was read, and then, the summary of the remaining articles. After that, the articles that remained were read in full.

From the articles that were selected after full reading, the following data were identified for posterior analysis: number, gender and age of the participants; type of tumor; audiological procedures employed; drug(s) used, cycle and dose; hearing loss criteria; follow-up; main audiological findings; evidence of ototoxicity. Conflicts in the analysis of the studies were solved by discussion between the researchers.

For the assessment of risk of bias in each study, the Cochrane19 tool was used, which encompasses the following criteria: randomization; allocation concealment; blinding of participants; blinding of outcome assessor; incomplete outcomes; selective outcome reports; and other sources of bias. Each individual criterion was considered as having low risk of bias, high risk of bias, or uncertain risk of bias (lack of information, or uncertainties referring to potential biases). The discrepancies between the authors were solved by consensus.

Literature Review

Results in the Electronic Databases

A total of 3,625 studies were found throughout the databases researched. Among these, 2,415 studies were repeated and so they were excluded.

The titles of the remaining 1,210 articles were read, leading to the exclusion of 622 due to their digressing from the topic approached in this review, so that 588 remained, whose summaries were read.

After the reading of the summaries, 186 articles of interest were left, which were fully read. Of these, 163 did not meet all the criteria for this research.

Lastly, 23 articles met all the inclusion criteria and answered the research question; hence, they were considered for analysis in this review. The flowchart with the stages in the selection of the articles can be visualized in Figure 1. The main aspects of the selected studies are found in Figures 2 and 3.

Legend: PTA: Pure-tone audiometry; OAE: Otoacoustic emissions; TEOAE: Transient evoked otoacoustic emissions; DPOAE: Distortion-product otoacoustic emissions; SOAE: Spontaneous otoacoustic emissions; BAEP: Brainstem auditory evoked potentials; ASHA: American Speech-Language-Hearing Association; POGT: Pediatric Oncology Group Toxicity; BHL: Bilateral Hearing Loss; NS: Not specified in the article; TCD: Total cumulative dose.

Figure 1: Flowchart of the selection stages of articles found in the literature 

Legend: PTA: Pure-tone audiometry; OAE: Otoacoustic emissions; TEOAE: Transient evoked otoacoustic emissions; DPOAE: Distortion-product otoacoustic emissions; HL: Hearing loss; SNHL: Sensorineural hearing loss; ASHA: American Speech-Language-Hearing Association; POGT: Pediatric Oncology Group Toxicity; BHL: Bilateral Hearing Loss; NS: Not specified in the article.

Figure 2: Summary of the main methodological aspects of the selected articles 

Figure 3: Summary of the main results of the selected articles 

Analysis of the Selected Studies

There is in the literature a concern regarding the ototoxic effects in children with cancer submitted to platinum-based chemotherapy, since the administration of these substances can impair the functioning of the structures of the auditory system. Even though only 23 studies met all the inclusion criteria, it was observed in the first stages of the research a great number of articles verifying the chemotherapy effects on hearing.

Regarding the risk of bias (Figure 4), all the studies included presented methodological flaws in at least one criterion evaluated. In all the studies, a high risk of bias was noted in the criteria of randomization, allocation concealment, blinding of participants and blinding of outcome assessors, which may be justified by the type of population assessed and treatment conducted. As for the criterion of incomplete outcomes, all the studies presented low risk of bias, since all data loss was justified, and the outcomes lost did not influence on the effect size observed. For the criterion selective outcome reports, five studies presented uncertain risk of bias, for the information was insufficient to enable it to be judged. Nine studies presented other sources of bias, the main one being the absence of information regarding the use of concomitant medications.

Figure 4: Analysis of the risk of bias of the selected articles 

Chemotherapy Drugs and Types of Tumors

Concerning the drug used in chemotherapy treatment, nine studies (39.13%) assessed the effect of cisplatin alone12,20-27, with doses ranging from 50 to 160 mg/m2 per cycle (cycles between 1 and 6); five studies (21.74%) assessed carboplatin alone28-32, with doses ranging from 322 to 2,210 mg/m2 per cycle (cycles between 1 and 9); and, nine studies (39.13%) assessed the effects of cisplatin and/or carboplatin4,8,33-39. Of the studies with cisplatin and/or carboplatin, the majority does not mention the number of cycles and/or the doses of each drug per cycle; the total cumulative dose of cisplatin ranged from 20 to 1,000 mg/m2, whereas that of carboplatin ranged from 104 to 15,550 mg/m2.

Regarding the types of tumors included, five studies (21.74%) were limited to studying individuals diagnosed with retinoblastoma28-32. The other studies considered various other types of tumors, the most common being: neuroblastoma, medulloblastoma, osteosarcoma, hepatoblastoma, sarcoma, carcinoma, glioma, central nervous system tumor, and germ-cell tumor.

Methodological Characteristics

The sample number varied greatly, as there were studies that assessed only 10 individuals31,32, whereas another one assessed 451 individuals38 (80.72 ± 109.99).

Regarding gender, only two studies 4,30 did not mention the distribution of the participants. Most of them included children and adolescents of both genders, similarly distributed (mean number of female individuals per study: 39.8 ± 57.6; and male individuals: 35.95 ± 55.4).

The mean age at diagnosis also varied considerably between the various studies, from seven months28 to 12.3 years22.

Considering that the aim of this research was to verify the effects of cisplatin and carboplatin chemotherapy on the auditory system of children and/or adolescents with cancer, the selected studies tended to be longitudinal, assessing the individuals before, during and/or after chemotherapy; the follow-up after chemotherapy ranged from one month to 127 months. Only five studies performed the assessment exclusively post-chemotherapy treatment4,22,27,29,36.

Among the studies, different methods were employed to compose the audiological assessment. Since a wide age range was involved in the assessment, sometimes including very small children, the auditory assessment method had to be adapted to the child’s response possibilities; therefore, for some of the studies, objective and/or subjective procedures had to be used8,12,20,28,30,33,39.

Four studies used only the pure-tone audiometry (conventional, conditioned or with visual reinforcement)4,26,35,38, and only one considered high-frequency audiometric assessment33.

The acoustic immittance, though used in many of the studies12,20,24,27,28,31,35, was carried out mainly with the purpose of discarding possible middle ear alterations that could compromise the results of the other procedures, especially those of the otoacoustic emissions (OAE).

Of the 17 studies that assessed auditory functioning through the OAE, only one made use of spontaneous OAE25. Three studies used transient evoked otoacoustic emissions (TEOAE)20,29,32, three used distortion-product otoacoustic emissions (DPOAE)8,31,33, and eight used both procedures12,21-24,28,36,37; in two of the studies, it was not possible to specify the type of stimulus used30,34.

The OAE, besides being an objective method, an alternative to behavioral auditory assessment, had its inclusion justified by some authors for its potential in assessing outer hair cells function in patients submitted to chemotherapy, capable of providing early evidences of cochlear damage, even before the occurrence of alterations on auditory thresholds obtained through pure-tone audiometry22,32,36,39.

Some studies also included the brainstem auditory evoked potentials (BAEP)8,12,20,28,30,33,39; however, the usefulness of this procedure was mostly in estimating the psychoacoustic threshold of babies and very small children, who are not able to respond to behavioral assessments. Of the seven studies that used the BAEP8,12,20,21,28,33,39, only one described the findings from such assessment20.

In addition to the diversity of procedures, there was also a diversity of criteria used for classifying hearing loss and/or detecting ototoxicity. Two studies considered as hearing loss auditory thresholds superior to 20 dB HL, without mentioning any other specific criterion24,25. Other studies also used 20 dB HL as hearing loss criterion, besides including specific criteria to identify the presence of ototoxicity, such as: Common Terminology Criteria for Adverse Events26; Brock grading system8,35; ASHA’s criteria referring to ototoxicity19,34,37; Muenster criteria38; SIOP Boston ototoxicity scale39; and a comparison between diverse criteria (ASHA, Brock, Muenster, POGT, BHL)4,12,33. On the other hand, ten studies did not specify the criterion used to classify hearing loss and/or presence of ototoxicity20,22,23,27-32,36.

The absence of this criterion for the classification of hearing loss due to ototoxicity may be justified by the variety of methods used in audiological assessment, since not carrying out the pure-tone audiometry makes it unfeasible to use many of these standardized criteria, as most of them are based on auditory thresholds and/or on evolution throughout time.

A recent literature review on the subject40 assessed the most used criteria for ototoxicity, discussing their benefits and limitations. The authors observed that diverse criteria are used in the various studies, including some verified in this study: ASHA, Brock, Muenster, SIOP, among others. The authors concluded that the different ototoxicity criteria result in different prevalence and degrees of hearing loss, which may result in different medical practice. Moreover, attention was called to the need of further research on the subject, emphasizing the importance of adopting a consensual criterion to follow up chemotherapy regimens, as well as the inclusion of high-frequency audiometry (>8 kHz) and/or auditory assessment through OAE.

Results of the Audiological Assessment and Occurrence of Ototoxicity

The methodological differences between the studies (different audiological procedures, time of assessment, as well as the use of different classification criteria) resulted in a great variability between the 23 studies. Despite this, in regard to prevalence or incidence of hearing loss, it can be concluded that most of the studies (82.6%) verified the occurrence of ototoxicity in children and adolescents submitted to platinum-based medication treatment.

Of the 19 studies that verified ototoxic effects during or after the treatment with the antineoplastic agents used, nine included only cisplatin, whereas the others studied cisplatin and/or carboplatin.

Regarding cisplatin, it was noted that auditory impairment could already be verified right after the first chemotherapy dose, with absence or decrease of the OAE in 7.6% of the individuals24, as well as significant changes of high-frequency auditory thresholds, and decrease in OAE, in approximately 50% of the individuals21.

Similarly, another study identified that 25% of the individuals already presented sensorineural hearing loss right after the first cycle of cisplatin (cumulative doses of 120 to 160 mg/m2). Furthermore, 16.6% of the individuals developed hearing loss after the second cycle of cisplatin (cumulative doses of 200 to 320 mg/m2) and 8.3% of the individuals presented hearing loss after the third cycle of cisplatin (cumulative doses of 360 mg/m2)12.

In addition to the immediate effect, other studies highlighted that the appearance of hearing loss may happen even after the cisplatin treatment has finished, justifying the importance of audiological monitoring even after the end of the treatment. One of the studies analyzed in this review observed that 26% of the individuals presented high-frequency sensorineural hearing loss, whose appearance began from one to 60 months after the end of the chemotherapy, regardless of individual or cumulative doses of cisplatin20. Another three studies also verified percentages of alterations ranging from 24 to 100%, from 6 to 44 months after, the main hearing loss being the sensorineural, bilateral and symmetric22,23,25-27.

As for the studies that assessed carboplatin and/or cisplatin, all of them verified ototoxic effects of the drug(s), there being found prevalence of auditory alterations ranging from 17 to 94%4,8,33-39, including decreased amplitude of OAE and/or hearing loss of various degrees, involving mainly the high frequencies.

Two of these studies also specified the prevalence of alterations related to each drug38,39. The first study verified 45% of alterations in individuals treated only with cisplatin, 17% of those treated only with carboplatin, and 75% of the ones treated with both agents38. As for the second study, there was a prevalence of 25% those treated only with cisplatin; 19% of those treated only with carboplatin, and 35% of the individuals that underwent combined treatment (cisplatin and carboplatin)39. Despite the differences in prevalence, it was observed that carboplatin presented a less ototoxic effect, followed by cisplatin, whereas the combined use of the two substances presented greater ototoxic power due to its synergistic effect.

Not all the studies described systematically the hearing loss characteristics in children with cancer, due to the different methodological procedures/ classification criteria employed, as previously mentioned. Nevertheless, in the studies that described these variables, it was noted that the audiological profiles were very similar after the chemotherapy treatment. There was a prevalence of sensorineural hearing loss12), (20,21,27,39, of mild to moderate degree, bilateral and symmetric in most of the cases21,27, affecting mainly the high frequencies12), (20-23,25,36, although some studies also observed the presence of severe degree of hearing loss in some patients8,26,36,39.

The high-frequency audiometry analysis (between 9 and 16 kHz), which was used in only one study, showed 94.1% of bilateral ototoxicity in this frequency range33. Likewise, the studies revealed a decrease in the amplitude of responses to the OAE, both by transient stimuli and distortion product, the high frequencies being more sensitive to ototoxic action21,22,24,31,33. The analysis of the responses to the OAE was compatible with the results presented in the pure-tone audiometry20,24, which highlights that the basal regions of the cochlea are the most affected33.

It is described in the literature that the platinum-based compounds affect first the outer hair cells at the basal region of the cochlea, which is the reason for it initially affecting frequencies over 4,000 Hz24,31.

Regarding the brainstem auditory pathway analysis, the only study that described this finding (registered in seven patients) observed an increase of the wave V latency at the intensity of 20 dBnHL in an individual, suggesting a cochlear dysfunction, and an increase of the interpeak in two individuals, suggesting a neural-conduction slowdown along the auditory nerve. This is the only study of those selected for this review that highlighted the possibility of retrocochlear alteration as a result of the cisplatin20.

Hence, future studies are necessary to consider the auditory pathway integrity analysis through the BAEP, and to assess the possibility of neurotoxicity resulting from the use of chemotherapy medications.

Five studies assessed only individuals with retinoblastoma, treated with carboplatin alone28-32. Of these, only one study observed decrease in DPOAE at the frequency of 7,996 Hz in 40% of the individuals, which indicates ototoxicity31; in the other four studies, no ototoxic effects resulting from chemotherapy were observed28-30,32. Some other studies have reported that carboplatin alone may not cause alterations in the auditory pathways8,36; nonetheless, cumulative doses are potentially ototoxic31.

When observing the cumulative doses in these five studies28-32, administration of high doses was not observed in the study that observed ototoxicity31 in comparison to the other ones28-30,32. Therefore, though countless other factors may have interfered in these results, it cannot be discarded the influence that even small doses may have on impairing the functioning of the cochlear hair cells.

In the case of children with retinoblastoma, one of the studies highlighted the priority of early detection of ototoxicity, since many children are diagnosed after presenting visual impairment. If the ototoxic potential is identified in due time, the dosage of carboplatin and/or other drugs can be changed to avoid further cochlear deterioration, considering that the negative impacts of hearing loss can be even more aggressive in a child with visual impairment28.

Among the most highlighted factors of great risk of developing platinum-induced hearing loss, the diagnosis of osteosarcoma26 and the cumulative cisplatin dosage can be cited8,20,22,27, being this greater than 400 mg/m²26, though dosages superior to 200 mg/m² have already shown to be ototoxic12. The influence of age has also been mentioned, as well as the concomitant use of furosemide38.

Considering this, it is fundamental that audiological monitoring be carried out in this population, before, during and after the treatment, emphasizing the need of long-term follow-up, as well.

Auditory monitoring can aid in decision-making related to the treatment itself and/or in determining the appropriate clinical interventions for each case, seeking to minimize possible negative impacts of hearing loss for the language, schooling and quality of life of these individuals.

Regarding the evaluative procedures, the instrument should be adapted to child’s response possibilities. Nevertheless, whenever possible, conducting pure-tone threshold audiometry is desirable, as most of the time the auditory thresholds are gold standard for ototoxicity monitoring in the many criteria available.

Furthermore, the inclusion of the OAE and/or the high-frequency audiometry (>8 kHz) is fundamental, since these are clinical resources capable of showing possible auditory impairments even before any alteration is observed on the conventional pure-tone audiometry, due to the damage beginning at the basal region of the cochlea.

In this study, the possible role of genetics on determining ototoxicity was not discussed, neither was the use of otoprotective agents for hearing loss in this population. Future studies on the subject should be conducted, deepening knowledge about these specific issues.


The studies demonstrated a high incidence of sensorineural hearing loss, mainly at high frequencies, as well as absence or decrease of OAE response amplitude, suggesting important cochlear impairment, especially at the basal regions of the cochlea, which can be already triggered after the first dose of chemotherapy, to which carboplatin seems to have a smaller ototoxic effect than does cisplatin.

The effects of ototoxicity on the central auditory pathways are not yet clear, so future research should consider post-chemotherapy central auditory nervous system integrity assessment.

The development of specific protocols for the identification of hearing loss is necessary, considering the age of the individuals and, consequently, the audiological procedures to be used. Such aspect would aid in adopting specific criteria for the identification of ototoxicity, thus, facilitating the audiological monitoring, the comparison between different studies and the medical practice.


1. Instituto Nacional de Câncer José Alencar Gomes da Silva. Coordenação de Prevenção e Vigilância Estimativa 2016: incidência de câncer no Brasil / Instituto Nacional de Câncer José Alencar Gomes da Silva - Rio de Janeiro: INCA, 2015. Disponível em: [ Links ]

2. DeVita VT Jr, Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68(21):8643-53. [ Links ]

3. Warwick GP. The mechanism of action of alkylating agents. Cancer Res. 1963;23:1315-33. [ Links ]

4. Silva AM, Latorre MRDO, Cristofani LM, Odone Filho V. The prevalence of hearing loss in children and adolescents with cancer. Braz J Otorhinolaryngol. 2007;73(5):608-14. [ Links ]

5. 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:CD009219. [ Links ]

6. Rybak LP, Whitworth CA. Ototoxicity: therapeutic opportunities. Drug Discov Today. 2005;10(19):1313-21. [ Links ]

7. van As JW, van den Berg H, van Dalen EC. Platinum-induced hearing loss after treatment for childhood cancer. Cochrane Database Syst Rev. 2016 Aug 3:CD010181. [ Links ]

8. Bertolini P, Lassalle M, Mercier G, Raquin MA, Izzi G, Corradini N et al. Platinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss. J Pediatr Hematol Oncol. 2004;26(10):649-55. [ Links ]

9. Almeida EOC, Umeoka WG, Viera RC, Moraes FI. High frequency audiometric study in cancer-cured patients treated with cisplatin. Braz J Otorhinolaryngol. 2008;74(3):382-90. [ Links ]

10. Stöhr W, Langer T, Kremers A, Bielack S, Lamprecht-Dinnesen A, Frey E et al. Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system. Cancer Invest. 2005;23(3):201-7. [ Links ]

11. Li Y, Womer RB, Silber JH. Predicting cisplatin ototoxicity in children: in influence of age and cumulative dose. Eur J Cancer. 2004;40(16):2445-51. [ Links ]

12. Lanvers-Kaminsky C, Krefeld B, Dinnesen AG, Deuster D, Seifert E, Würthwein G et al. Continuous or repeated prolonged cisplatin infusions in children: a prospective study on ototoxicity, platinum concentrations, and standard serum parameters. Pediatr Blood Cancer. 2006;47(2)183-93. [ Links ]

13. Dean JB, Hayashi SS, Albert CM, King AA, Karzon R, Hayashi RJ. Hearing loss in pediatric oncology patients receiving carboplatin-containing regimens. J Pediatr Hematol Oncol. 2008;30(2):130-4. [ Links ]

14. Ding D, Allman BL, Salvi R. Review: ototoxic characteristics of platinum antitumor drugs. Anat Rec (Hoboken). 2012;295(11):1851-67. [ Links ]

15. Stern JN, Bunin N. Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors. Med Pediatr Oncol. 2002;39(3):163-7. [ Links ]

16. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Ann Intern Med. 2009:151(4):264-9. [ Links ]

17. Santos CMC, Pimenta CAM, Nobre MRC. The PICO strategy for the research question construction and evidence search. Rev Lat Am Enfermagem. 2007;15(3):508-11. [ Links ]

18. Oxford Centre for Evidence-based Medicine - Levels of Evidence. Março de 2009. Disponível em: Acesso em: 01 de Agosto de 2016. [ Links ]

19. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ.2011;343:d5928. [ Links ]

20. Berg AL, Spitzer JB, Gamin JH. Ototoxic impact of cisplatin in pediatric oncology patients. Laryngoscope. 1999;109(11):1806-14. [ Links ]

21. Stavroulaki P, Apostolopoulos N, Segas J, Tsakanikos M, Adamopoulos G. Evoked otoacoustic emissions - an approach for monitoring cisplatin induced ototoxicity in children. Int J Pediatr Otorhinolaryngol. 2001;59(1):47-57. [ Links ]

22. Coradini PP, Cigana L, Selistre SG, Rosito LS, Brunetto AL. Ototoxicity from cisplatin therapy in childhood cancer. J Pediatr Hematol Oncol. 2007;29(6):355-60. [ Links ]

23. Schmidt CM, Knief A, Lagosch AK, Deuster D, Zehnhoff-Dinnesen A. Left-right asymmetry in hearing loss following cisplatin therapy in children--the left ear is slightly but significantly more affected. Ear Hear. 2008;29(6):830-7. [ Links ]

24. Al-Noury K. Distortion product otoacoustic emission for the screening of cochlear damage in children treated with cisplatin. Laryngoscope. 2011;121(5):1081-4. [ Links ]

25. Weissenstein A, Deuster D, Knief A, Zehnhoff-Dinnesen AA, Schmidt CM. Progressive hearing loss after completion of cisplatin chemotherapy is common and more pronounced in children without spontaneous otoacoustic emissions before chemotherapy. Int J Pediatr Otorhinolaryngol. 2012;76(1):131-6. [ Links ]

26. Castelán-Martínez OD, Jiménez-Méndez R, Rodríguez-Islas F, Fierro-Evans M, Vázquez-Gómez BE, Medina-Sansón A et al. Hearing loss in Mexican children treated with cisplatin. Int J Pediatr Otorhinolaryngol. 2014;78(9):1456-60. [ Links ]

27. Liberman PH, Goffi-Gomez MV, Schultz C, Novaes PE, Lopes LF. Audiological profile of patients treated for childhood cancer. Braz J Otorhinolaryngol. 2016;82(6):623-9. [ Links ]

28. Smits C, Swen SJ, Goverts ST, Moll AC, Imhof SM, Meeteren AYNS. Assessment of hearing in very young children receiving carboplatin for retinoblastoma. Eur J Cancer. 2006;42(4):492-500. [ Links ]

29. Amorim AM, Azevedo MF, Carvalho CAF, Macedo CRPD. Transient otoacoustic emissions in childrens with retinoblastoma submitted to chemiotherapy with carboplatin. Int Arch Otorhinolaryngol. 2007;11(4):375-9. [ Links ]

30. Lambert MP, Shields C, Meadows AT. A retrospective review of hearing in children with retinoblastoma treated with carboplatin-based chemotherapy. Pediatr Blood Cancer. 2008;50(2):223-6. [ Links ]

31. Bhagat SP, Bass JK, White ST, Qaddoumi I, Wilson MW, Wu J et al. Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma. Int J Pediatr Otorhinolaryngol. 2010;74(10):1156-63. [ Links ]

32. Bhagat SP, Bass JK, Qaddoumi I, Brennan R, Wilson M, Wu J et al. Time-frequency analysis of transient-evoked otoacoustic emissions in children exposed to carboplatin chemotherapy. Audiol Neurootol. 2013;18(2):71-82. [ Links ]

33. Knight KR, Kraemer DF, Winter C, Neuwelt AE. Early changes in auditory function as a result of platinum chemotherapy: use of extended high-frequency audiometry and evoked distortion product otoacoustic emissions. J Clin Oncol. 2007;25(10):1190-5. [ Links ]

34. Al-Khatib T, Cohen N, Carret AS, Daniel S. Cisplatinum ototoxicity in children, long-term follow up. Int J Pediatr Otorhinolaryngol. 2010;74(8):913-9. [ Links ]

35. Einarsson EJ, Petersen H, Wiebe T, Fransson PA, Grenner J, Magnusson M et al. Long term hearing degeneration after platinum based chemotherapy in childhood. Int J Audiol. 2010;49(10):765-71. [ Links ]

36. Einar-Jon E, Trausti O, Asgeir H, Christian M, Thomas W, Måns M et al. Hearing impairment after platinum-based chemotherapy in childhood. Pediatr Blood Cancer. 2011;56(4):631-7. [ Links ]

37. Peleva E, Emami N, Alzahrani M, Bezdjian A, Gurberg J, Carret A et al. Incidence of platinum-induced ototoxicity in pediatric patients in Quebec. Pediatr Blood Cancer. 2014;61(11):2012-7. [ Links ]

38. Clemens E, Vries AC, Pluijm SF, Am Zehnhoff-Dinnesen A, Tissing WJ, Loonen JJ et al. Determinants of ototoxicity in 451 platinum-treated Dutch survivors of childhood cancer: A DCOG late-effects study. Eur J Cancer. 2016;69:77-85. [ Links ]

39. Fetoni AR, Ruggiero A, Lucidi D, De Corso E, Sergi B, Conti G et al. Audiological monitoring in children treated with platinum chemotherapy. Audiol Neurootol. 2016;21(4):203-11. [ Links ]

40. Waissbluth S, Peleva E, Daniel SJ. Platinum-induced ototoxicity: a review of prevailing ototoxicity criteria. Eur Arch Otorhinolaryngol. 2017;274(3):1187-96. [ Links ]

1Project carried out at the Departamento de Fisioterapia, Fonoaudiologia e Terapia Ocupacional da Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, São Paulo, Brazil.


In the article, “Effects of chemotherapy on the auditory system of children with cancer: a systematic literature review”, with DOI number: 10.1590/1982-0216/202022213919, published in the journal Revista Cefac 2020;22(2):e13919, in the author’s name (page 1):

Where it was:

Nila Berbardes Lopes


Nila Bernardes Lopes

Received: September 09, 2019; Accepted: November 29, 2019

Corresponding address: Liliane Aparecida Fagundes Silva, Rua Cipotânea, 51, Cidade Universitária, CEP: 05360-160 - São Paulo, São Paulo, Brasil, E-mail:

Conflict of interests: Nonexistent

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