Cisplatin-associated ototoxicity amongst cervical cancer patients: A prospective cohort study in south Africa

PLoS One. 2023 Apr 4;18(4):e0283639. doi: 10.1371/journal.pone.0283639. eCollection 2023.

Abstract

Background: Concurrent chemoradiotherapy using weekly cisplatin remains standard of care for locally advanced cervical cancer in Sub-Saharan Africa. While cisplatin remains a popular cancer chemotherapeutic, it has an irreversible ototoxic effect on patients' auditory system. However, there is a paucity of epidemiological information on its extent and severity during cervical cancer treatment. In a region with a high burden of cervical cancer, this has serious consequences for aural intervention and rehabilitation.

Methods and findings: Using a prospective cohort study design, 82 patients with incident cervical cancer, receiving weekly cisplatin chemotherapy (50 mg/m2 body surface) at a tertiary level hospital in KwaZulu-Natal Province of South Africa, underwent audiological assessments at various intervals. We describe the temporal impact of cisplatin exposure on hearing loss, its combined effect with HIV-infection, and estimate ototoxicity incidence in this cohort. The median age was 52 years with Stages IIB (45%) and IIIB (35.4%) cancers being most common. Complaints of reduced hearing sensitivity increased significantly (p<0.0001). Bilateral, asymmetrical sensorineural hearing loss, with greater effect in the extended high-frequency range, was evident. Cisplatin dosage was significantly associated with ototoxicity severity at one- (p = 0.017), three- (p = 0.010), and six-month (p = 0.015) post-treatment follow-up. HIV-seropositivity (53.7%) was significantly associated with NCI-CTCAE Grading Scale at three- (p = 0.022) and six-months (p = 0.023) post-treatment. Multiple Tobit regression revealed a cumulative dose effect bilaterally, after adjustment for age and HIV status, evident from 9000Hz and above in the right ear, while a plateau effect was observed at 250mg/m2 in the left ear. The incidence was ototoxicity was 98% at a cumulative dose of 150mg/m2.

Conclusion: The findings of this epidemiologic study highlight the temporal course and severity of ototoxicity experienced by cervical cancer patients treated with cisplatin, with greater impact in HIV-positive subgroup, thus underscores the need for audiological monitoring and timely interventions in this cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Audiometry, Pure-Tone
  • Cisplatin / adverse effects
  • Female
  • HIV Infections* / drug therapy
  • Hearing Loss, Bilateral
  • Hearing Loss, Sensorineural* / epidemiology
  • Humans
  • Middle Aged
  • Ototoxicity* / epidemiology
  • Ototoxicity* / etiology
  • Prospective Studies
  • South Africa / epidemiology
  • Uterine Cervical Neoplasms* / drug therapy

Substances

  • Cisplatin
  • Antineoplastic Agents

Grants and funding

JP (the principal investigator) received the National Health Scholarship Grant facilitated by the South African Medical Research Council (https://www.samrc.ac.za/funding/grants-and-scholarships) for the purpose of freeing her from her employment to conduct data collection. Funding from Oticon Fonden (https://www.sdu.dk/en/om_sdu/fakulteterne/samfundsvidenskab/forskning/forskningsstoette/fonde+og+puljer/private+danske+fonde/oticon+fonden) was used for running expenses such as patient reimbursement, travelling expenses and purchase and calibration of equipment. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.