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

by Jessica Paken, Cyril Devadas Govender, Mershen Pillay, Merga Feyasa, Vikash Sewram

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.

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.

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.