Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study

Moke, Diana J.; Luo, Cheng; Millstein, Joshua; Knight, Keith; Rassekh, Shahrad R.; Brooks, Beth; Ross, Colin; Wright, Michael; Mena, Victoria; Rushing, Teresa; Esbenshade, Adam J.; Carleton, Bruce; Orgel, Etan

doi:10.1016/s2352-4642(21)00020-1

Cited by 49 publications

(67 citation statements)

References 29 publications

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“…This report supports a recent study published which also identified the amount per dose as a risk factor for hearing loss ( 24 ). Our study can be distinguished from that report due to the following differences.…”

Section: Discussionsupporting

confidence: 92%

“…Our mean time in years from the last CDDP administration to the last audiogram was 3.73 years while the previous study reported a mean of 1.5 years from the end of treatment. The increased prevalence of hearing loss as patients are followed longer and the use of the better verses worse ear may explain the difference in hearing loss observed by those investigators (43.8%) compared to our study (72.6%) (24).This late onset hearing loss particularly affects patients with established hearing loss at the completion of therapy. Thus, even mild and unilateral CDDP associated hearing loss is significant and warrants further follow-up.…”

Section: Discussioncontrasting

confidence: 57%

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Cisplatin Ototoxicity: Examination of the Impact of Dosing, Infusion Times, and Schedules In Pediatric Cancer Patients

et al. 2021

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BackgroundSensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss.MethodsA retrospective review of 993 pediatric patients’ medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical data including CDDP dosing information. Demographic and clinical characteristics were summarized by descriptive statistics, and univariate and multivariate logistic regressions were performed to examine the relationship between hearing loss and specific parameters of cisplatin administration (amount infused per dose, prescribed infusion time, total number of doses, number of doses per cycle, number of cycles, cumulative cisplatin exposure). Stepwise variable selection procedure was performed in the multivariate model building to extract the best subset of risk factors for the prediction of hearing loss and worsening ototoxicity grade using an established ototoxicity grading scale from the International Society of Pediatric Oncology (SIOP).ResultsA total of 153 patients with complete medical and audiologic data were evaluable for analysis. Hearing loss was identified in 72.6% of the patients. Multivariate analysis revealed that age [OR=0.90 (0.84-0.97), p-value=0.0086], radiation to any part of the body, [OR=3.20 (1.29-7.93), p-value=0.012], amount infused per dose (mg/m2) [OR=1.018 (1.002-1.033), p-value=0.029], and cumulative cisplatin exposure (mg/m 2) [OR=1.004 (1-1.008), p-value=0.027] were associated with hearing loss. Similar associations were also found between these risk factors and worsening SIOP grade.ConclusionIn one of the largest studies examining the influence of CDDP dosing and schedules on hearing loss, we found the amount of CDDP infused per dose is a significant risk factor. Considerations in designing regimens that reduce the amount of CDDP infused per dose may reduce the risk of hearing loss. Randomized prospective trials are needed.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 57%

Cisplatin Ototoxicity: Examination of the Impact of Dosing, Infusion Times, and Schedules In Pediatric Cancer Patients

et al. 2021

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Section: Discussionmentioning

confidence: 71%

“…Finally, we noted that the rate of SNHL in our sample aligns with a large multicenter study, conducted in a sample of 1481 patients who received cisplatin. 34 In this study, the authors demonstrated that 43.8% of all children treated for cancer developed cisplatin‐induced SNHL, and that rates were even higher for brain tumor patients (50.9%), and children treated <5 years (59.4%). Based on our findings, with significantly lower perceptual reasoning and working memory identified in children treated with chemotherapy only who experience severe SNHL, these children are at risk for school problems; low working memory can affect a child's concentration and ability to follow instructions, and low perceptual reasoning can render a child less capable of using effective problem‐solving strategies.…”

Section: Discussionmentioning

confidence: 75%

Hearing loss and intellectual outcome in children treated for embryonal brain tumors: Implications for young children treated with radiation sparing approaches

et al. 2021

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“…Moreover, as CDDP is commonly used for the therapy of NB [9][10][11]51] and soft tissue malignancies, including RMS [52][53][54], the combination of CDDP/EB5 supports the rationale for the usefulness of Bet derivatives combined with CDDP in the future development of novel therapeutic schedules. This kind of approach may potentially overcome frequently observed drug resistance and could result in the enhancement of anti-cancer activity and the reduction in toxicity and adverse effects [10,108] by a significant decrease in CDDP doses in clinical use. However, the pharmacological type of interactions between ASBDs and CDDP requires further analysis.…”

Section: Discussionmentioning

confidence: 99%

Acetylenic Synthetic Betulin Derivatives Inhibit Akt and Erk Kinases Activity, Trigger Apoptosis and Suppress Proliferation of Neuroblastoma and Rhabdomyosarcoma Cell Lines

Król

Bębenek

Dmoszyńska‐Graniczka

et al. 2021

IJMS

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Neuroblastoma (NB) and rhabdomyosarcoma (RMS), the most common pediatric extracranial solid tumors, still represent an important clinical challenge since no effective treatment is available for metastatic and recurrent disease. Hence, there is an urgent need for the development of new chemotherapeutics to improve the outcome of patients. Betulin (Bet), a triterpenoid from the bark of birches, demonstrated interesting anti-cancer potential. The modification of natural phytochemicals with evidenced anti-tumor activity, including Bet, is one of the methods of receiving new compounds for potential implementation in oncological treatment. Here, we showed that two acetylenic synthetic Bet derivatives (ASBDs), EB5 and EB25/1, reduced the viability and proliferation of SK-N-AS and TE671 cells, as measured by MTT and BrdU tests, respectively. Moreover, ASBDs were also more cytotoxic than temozolomide (TMZ) and cisplatin (cis-diaminedichloroplatinum [II], CDDP) in vitro, and the combination of EB5 with CDDP enhanced anti-cancer effects. We also showed the slowdown of cell cycle progression at S/G2 phases mediated by EB5 using FACS flow cytometry. The decreased viability and proliferation of pediatric cancers cells after treatment with ASBDs was linked to the reduced activity of kinases Akt, Erk1/2 and p38 and the induction of apoptosis, as investigated using Western blotting and FACS. In addition, in silico analyses of the ADMET profile found EB5 to be a promising anti-cancer drug candidate that would benefit from further investigation.

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Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study

Cited by 49 publications

References 29 publications

Cisplatin Ototoxicity: Examination of the Impact of Dosing, Infusion Times, and Schedules In Pediatric Cancer Patients

Cisplatin Ototoxicity: Examination of the Impact of Dosing, Infusion Times, and Schedules In Pediatric Cancer Patients

Hearing loss and intellectual outcome in children treated for embryonal brain tumors: Implications for young children treated with radiation sparing approaches

Acetylenic Synthetic Betulin Derivatives Inhibit Akt and Erk Kinases Activity, Trigger Apoptosis and Suppress Proliferation of Neuroblastoma and Rhabdomyosarcoma Cell Lines

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