One common side effect of cisplatin chemotherapy is ototoxicity. The drugs sodium thiosulfate and mannitol may protect against cisplatin-induced hearing loss. Specifically, sodium thiosulfate has been found to protect the cells in the inner ear, and may therefore prevent hearing loss. Mannitol can help sodium thiosulfate enter the inner ear, and ponteially increase the effectiveness of sodium thiosulfate. This study aims to assess the efficacy of sodium thiosulfate and mannitol to reduce the hearing impairment caused by cisplatin chemotherapy.

Randomized phase II clinical trial: with 1:1 randomization between cisplatin alone, and cisplatin + sodium thiosulfate and mannitol. Participants will first be recruited into a 2-year pilot feasibility study of 24 patients (12 in each arm). The pilot study will be performed to evaluate the feasibility of the trial as defined by the following factors: treatment outcomes, occurrence of adverse events, logistics of treatment delivery, as well as dropout and recruitment rates. The results from the pilot study will support the safety, efficacy, and effectiveness of the sodium thiosuldate and mannitol treatment, confirm feasibility using the factors mentioned above, and serve as an earlier-phase developmental function to enhance the probability of success of the subsequent clinical trial. Participants will complete various pre-treatment hearing tests. Participants will receive sodium thiosulfate and mannitol 4 - 8 hours following chemotherapy treatment. The control group will not receive the experimental intervention. Follow-up hearing tests will be performed at select time intervals following completion of their cancer treatment.

Inclusion Criteria:

• Patients undertaking systemic cisplatin therapy as part of their cancer treatment
• Age ≥ 18
• Willing to provide informed consent
• ECOG performance status 0-2
• For female of child-bearing potential, a negative pregnancy test (beta-HCG) prior to study treatment is required
• Any patient who is of reproductive age should provide written agreement to use adequate contraception for the duration of the trial

Exclusion Criteria:

• Age less than 18
• Preexisting severe to profound sensorineural hearing loss (unilateral or bilateral) (speech reception threshold >70dB, or word recognition score <50%) as confirmed with an audiogram
• History of Meniere's or fluctuating hearing loss
• Asymmetrical hearing loss (bone conduction threshold difference of: (a) 20 dB threshold difference at a single frequency, (b) 15 dB threshold difference at 2 frequencies, (c) 10 dB threshold difference at 3 frequencies
• Abnormal renal function (creatinine clearance <60 ml/min)
• Abnormal liver function (liver function tests (ALT and ALP) >2.5 times upper limit of normal without liver metastasis and >5 times upper limit of normal with liver metastasis
• Previous hypersensitivity to STS or mannitol
• Pregnant and/or nursing women
• Patient unable to follow the protocol for any reason