Ototoxic effects of antineoplastic drugs: a systematic review

Patatt, Fernanda Soares Aurélio; Gonçalves, Laura Faustino; Paiva, Karina Mary de; Haas, Patrícia

doi:10.1016/j.bjorl.2021.02.008

Acessibilidade / Reportar erro

Brasil

Brazilian Journal of Otorhinolaryngology

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Review article • Braz. j. otorhinolaryngol. 88 (01) • 2022 • https://doi.org/10.1016/j.bjorl.2021.02.008 copy

Ototoxic effects of antineoplastic drugs: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction

Platinum-based chemotherapeutics play an important role in the treatment of cancer at different levels and are the most cited ototoxic agents when scientific evidence is analyzed.

Objective

To present scientific evidence based on a systematic literature review, PRISMA, in order to systematize information on the ototoxic effects of using antineoplastic drugs.

Methods

For the selection of studies, the combination based on the Medical Subject Heading Terms (MeSH) was used. The Medline (Pubmed), LILACS, SciELO, SCOPUS, WEB OF SCIENCE and BIREME databases were used, without restriction of language, period, and location. Evaluation of the quality of the articles was carried out, which included articles with a minimum score of 6 in the modified scale of the literature. The designs of the selected studies were descriptive, cohort, and cross-sectional, which were related to the research objective.

Results

Three articles were included in this systematic review. The ototoxicity caused by cisplatin alone varied from 45% to 83.3%, while that caused by the use associated with carboplatin varied from 16.6% to 75%. There was a significant variation in the cumulative doses of these antineoplastic agents, both in isolated and in combination. Auditory changes, especially at high frequencies, were evident after completion of treatment.

Conclusion

Auditory changes after the use of platinum-based antineoplastic drugs were found, however, there was an important heterogeneity regarding the frequency of ototoxicity and the cumulative dose of the drugs used.

Keywords
Antineoplastic drugs; Hearing; Ototoxicity; Cisplatin; Exposure

Acronym	Definition
P	Patients
I	Antineoplastic
C	Medication
O	Ototoxicity
S	Descriptive study
	Cross-sectional study
	Case reports
	Case-control studies
	Controlled clinical trials
	Cohort studies

Inclusion criteria
Design	Cross-sectional study
	Case-control studies
	Cohort studies
	Case reports
	Intervention studies
	Controlled clinical trials
Localization	Without restriction
Language	Without restriction

Exclusion criteria
Design	Letter to the editor
	Guidelines
	Literature review
	Systematic review
	Narrative review
	Meta-analysis
Studies	Unclear studies
Studies	Poorly described or inadequate
Form of publication	Abstract only

Descriptors	Nº	Excluded references	Reason	Selected	Database
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	7	4	Excluded by title (2); excluded by abstracts (1); excluded by repetition (1).	3	Pubmed
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	0	0	-	0	Lilacs
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	0	0	-	0	Scielo
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	0	0	-	0	WEB OF SCIENCE
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up Studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	0	0	-	0	Bireme
(ototoxicity) AND (antineoplasic) AND (adults) AND (Childhood) AND (adolescent) AND (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized controlled trials[mh] OR random allocation[mh] OR double-blind method[mh] OR singleblind method[mh] OR clinical trial[pt] OR clinical trials[mh] OR (“clinical trial”[tw]) OR ((singl[tw] OR doubl[tw] OR trebl[tw] OR tripl[tw]) AND (mask[tw] OR blind[tw])) OR (“latin square”[tw]) OR placebos[mh] OR placebo[tw] OR random[tw] OR research design[mh:noexp] OR follow-up studies[mh] OR prospective studies[mh] OR cross-over studies[mh] OR control[tw] OR prospectiv[tw] OR volunteer*[tw]) NOT (animal[mh] NOT human[mh])	0	0	-	0	SCOPUS
Total	7	4		3	Pubmed

Author/year/place of publication	Objective	n	Tests	Hearing loss classification	Results	Conclusion
Einarsson et al.²⁷27 Einarsson JE, Petersen H, Wiebe T, Fransson AP, Grenner J, Magnusson M, et al. Long term hearing degeneration after platinum-based chemotherapy in childhood. Int J Audiol. 2010;49:765-71., 2010, Sweden	Investigate long-term hearing impairment in subjects who received platinum-based chemotherapy in childhood or adolescence.	15	PTA (0.125, 0.25, 0.5, 1, 2, 3, 4, 6 e 8 kHz)	Brock et al. (1991)	The results show that hearing loss, in subjects with ototoxicity, increased after the end of the treatment, also including the lower frequencies. The greatest deterioration in hearing thresholds, up to 55 dB HL, was found at frequencies above 2 kHz.	The conclusion of this study is that children and adolescents treated with platinum-based chemotherapy should undergo regular follow-up audiometric tests, also many years after the end of treatment. In addition, self-reported hearing impairment assessments should be made during and after chemotherapy
			Tympanometry Speech audiometry
			Measurement of the handicap level (Hearing measurement scale — HMS)
Clemens et al.²⁸28 Clemens E, Vries CHA, Zehnhoff-Dinnesenc A, Tissing JEW, Loonen JJ, Pluijm FMS, 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., 2016, Netherlands	To determine the frequency and determinants of ototoxicity in a large multicenter cohort of child cancer survivors who received platinum, but not cranial irradiation as treatment.	451	PTA (0.25, 0.5, 1, 2, 4 e 8 kHz)	Münster (Schmidt et al., 2007)	The general frequency of ototoxicity was 42%, observed in 45% of those treated with cisplatin, in 17% of those treated with carboplatin, and in 75% of those who received both drugs. The lowest age at the time of diagnosis, the highest total cumulative dose of cisplatin, and the concomitant treatment with furosemide were associated with ototoxicity.	Treatment with a higher total cumulative dose of cisplatin, younger age at diagnosis, and concomitant use of furosemide, independently, are associated with an increased risk of ototoxicity in subjects treated with platinum in childhood.
Clemens et al.²⁹29 Clemens E, Vries CHA, Zehnhoff-Dinnesenc A, Tissing JEW, Loonen JJ, Pluijm FMS, et al. Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors. J Pediatr Hematol Oncol. 2017:1-10., 2017, Netherlands	To study the reversibility of ototoxicity after discontinuing treatment in a cohort of subjects treated with platinum with hearing loss at the end of cancer treatment.	168	PTA (0.25, 0.5, 1, 2, 4 e 8 kHz): age ≥5 years	Münster (Schmidt et al., 2007)	Of the 168 participants, 61 (36.3%) had hearing loss after completing chemotherapy, and none of these subjects showed improvement in hearing function until 28.8 years after discontinuing treatment.	Ototoxicity after platinum treatment may be irreversible and monitoring, as well as longitudinal clinical haring care, is required.
			Conditioned play audiometry: age between 2 and 5 years.
			VRA in children aged 6 months to 2 years.

Authors (year)	Cumulative dose	Cumulative dose	Cumulative dose	Concomitant medications
	Cisplatin (n)	Carboplatin (n)	Cisplatin + carboplatin (n)
Einarsson et al.²⁷27 Einarsson JE, Petersen H, Wiebe T, Fransson AP, Grenner J, Magnusson M, et al. Long term hearing degeneration after platinum-based chemotherapy in childhood. Int J Audiol. 2010;49:765-71. (2010)	NHG: varied from 180 to 690 mg/m² (n = 5)	-	HLG: cisplatin = 320 mg/m², carboplatin = 3000 mg/m² (n = 1)	NCI
	HLG: ranged from 360 to 500 mg/m² (n = 8)	-		NCI
Clemens et al.²⁸28 Clemens E, Vries CHA, Zehnhoff-Dinnesenc A, Tissing JEW, Loonen JJ, Pluijm FMS, 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. (2016)	Ranged from 45 to 950 mg/m² (n = 276)	Ranged from 104 to 9436 mg/m² (n = 112)	Cisplatin = ranged from 80 to 570 mg/m², carboplatin = ranged from 400 to 6043 mg/m² (n = 63)	Vancomycin, gentamicin, tobramycin, furosemide (n = 285)
Clemens et al.²⁹29 Clemens E, Vries CHA, Zehnhoff-Dinnesenc A, Tissing JEW, Loonen JJ, Pluijm FMS, et al. Hearing loss after platinum treatment is irreversible in noncranial irradiated childhood cancer survivors. J Pediatr Hematol Oncol. 2017:1-10. (2017)^a a Only subjects with hearing loss were included.	Ranged from 180 to 900 mg/m² (n = 46)	Ranged from 1288 to 3230 mg/m² (n = 2)	Cisplatin = ranged from 300 to 570 mg/m², carboplatin = ranged from 992 to 3938 mg/m² (n = 13)	NI

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
E-mail: revista@aborlccf.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.