Sodium Thiosulfate
Five articles researched sodium thiosulfate for CiO prevention (Madasu et al., 1995, Ishikawa et al. 2015, Duinkerken et al., 2021, Zuur et al., 2007, Rolland et al., 2019). The first one was a prospective cohort of 70 patients with head and neck cancer, who received cisplatin, radiotherapy (dose not specified), and systemic sodium thiosulfate. The baseline audiometric analysis comparison to the audiometry after the fourth cisplatin infusion did not appear to confer sodium thiosulfate a protection hearing effect. Tinnitus or vestibular loss were not reported, nor were adverse reactions (Madasu et al., 1995). A similar prospective cohort of 18 patients with the same kind of cancer and receiving 60-70 Gray of radiotherapy assessed sodium thiosulfate otoprotection. The sodium thiosulfate group had significant hearing loss at ultra-high frequencies of 10 and 12 kHz (p = 0.028, 0.039, respectively), whereas the group not receiving sodium thiosulfate had significant hearing loss at high frequencies of 8 and 10 kHz (p = 0.016, 0.027, respectively). During follow-up, one patient presented with subjective tinnitus. Vertigo episodes and adverse reactions were not reported for any patient (Ishikawa et al. 2015). Later a pilot non-randomized control trial using transtympanic sodium thiosulfate in 12 adults for cisplatin and radiotherapy (maximum cochlear dose 30 Gray) was performed. The pure-tone average shift at 8 -12.5 kHz was 18.4 dB less in treated ears compared to untreated ears (p=0.068)(Duinkerken et al., 2021). This positive finding was further explored in a randomized control trial that tested intravenous sodium thiosulfate for CiO in 158 patients. All patients received concomitant radiotherapy (mean dose 70 Gray). In both treatment arms, the incidence of CiO did not deviate (P =0.14), but the intervention group had 10% less hearing loss at frequencies vital for speech perception (P = 0.001). No difference in adverse reactions between groups was observed (Zuur et al., 2007). Finally, a second randomized control trial tested trans-tympanic injections of sodium thiosulfate for CiO prevention in 13 patients with head and neck cancer. Although all of the patients received radiotherapy no dose information was provided. After 18 months of follow-up, the average hearing loss was 1.3 dB less for treated ears compared to control ears. Although not statistically (p = 0.61) nor clinically significant, the difference was in favor of the treated ears for all frequencies between 3 and 10 kHz. Injections caused dizziness in 3 patients, vertigo in one patient, and pain in 4 patients (Rolland et al., 2019).