Author Type of study & number of patients Type of Cancer Cisplatin dose Ototoxicity assessment Intervention Follow-up time Outcome Adverse Reactions
Gandara et al. 1995 RCT 214
Lung cancer Ovarian cancer
100 mg/m2
Clinical grading scale & audiometry
Diethyldithiocarbamate
Not reported
Patients in the intervention group had a greater but not significant reduction in auditory acuity at 3000 Hz(P = 0.095).
No difference between groups
Somlo et al. 1995 RCT 42 Sarcoma Breast
125 mg/m2
Audiometry
Dopamine infusion 2 ug/kg/min over 48 hours
1 month
No differences were observed in favor of the dopamine group when audiogram results were analyzed at 2,000, 4,000, or 8,000 Hz (P =0.27, 0.14, and 0.49, respectively).
Not reported
Kemp et al. 1996 RCT 242
Ovarian
100 mg/m2
Audiometry
Amifostine 910 mg/m2
41 months
Amifostine had a 43% reduction in the incidence of ototoxicity (P = 0.108) Ototoxicity required cisplatin dose reduction or discontinuation 16% in the control arm vs 9% in the amifostine arm.
Nausea and/or vomiting, hypotension, flushing, sneezing, dizziness, sleepiness, hiccups, and chills.
Madasu et al. 1997
Prospective Cohort 70
Head and neck
150 mg/m2
Audiometry
Sodium Thiosulfate
22 days
Sodium thiosulfate did not appear to confer protection. There were no cases of debilitating tinnitus or vestibular loss.
Not reported
Planting et al. 1999 RCT 74
Head and neck
70 mg/m2
Audiometry
Amifostine 740 mg/m2
6 months
Hearing loss was only seen at the high-frequencies (4000 and 8000 Hz). No difference in hearing or tinnitus occurrence (P = 0.24).
Hypotension, dizziness, flushing, anxiety, palpitations, sneezing.
Ekborn et al. 2004
Prospective Cohort 15
Melanoma Esophagus Cancer.
125 - 150 mg/m2
Audiometry
Amifostine 50 mg/mL
Not reported
92% of patients (11 of 12) had auditory symptoms. Ototoxicity was unacceptable despite amifostine treatment.
Nausea and vomiting, ototoxicity, neurotoxicity, oliguria, and hypotension.
Zuur et al. 2007 RCT 158
Head and neck
150 mg/m2
Audiometry
Intravenous Sodium Thiosulfate 9 g/m2 (30 minutes) followed by 12 g/m2 (2 hours)
3 months
Approximately 10% less hearing loss at frequencies vital for speech perception (P = 0.001).
No difference between groups
Yıldırım et al. 2010 RCT 54
Solid organ tumors
Not reported
Audiometry & auditory brainstem response
N-acetylcysteine 600 mg/day or salicylate 300 mg/day
2 months
Cisplatin-ototoxicity could be reduced in N-acetylcysteine group in 10,000 and 12,000 Hz (p<0.005) compared to placebo.
Not reported
Riga et al. 2013 RCT 20 Gastric Melanoma Head and neck Ewing Sarcoma Small cell lung cancer
50 - 100 mg/m2
Audiometry
Transtympanic N-acetylcysteine (10%)
Not reported
In treated ears no significant changes in auditory thresholds were recorded. In the control ears cisplatin induced a significant decrease of auditory thresholds at the 8000 Hz frequency band (P = 0.008).
Almost all patients had pain after application but it decreased gradually. One patient had an ear infection.
Yoo et al. 2014 RCT 11
Head and neck
100 mg/m2
Audiometry
Transtympanic L-N-Acetylcysteine (2%) 200mg/ml
2 months
The difference in hearing preservation did not reach significance.
Not reported
Marshak et al. 2014 RCT 26
Any cancer
517 mg/m2
Audiometry and DPOAE
Intratympanic Dexamethasone (10 mg/ml solution).
Not reported
Significant increase in the pure tone threshold for 6000 Hz was observed in the control (P<0.02) but not in the study group. Groups’ comparison showed a difference in the DPOAE average signal-to-noise ratio (P<0.04).
Slight pain and short mild vertigo during application
Ishikawa et al. 2015
Prospective Cohort 18
Head and neck
100 - 180 mg/m2
Audiometry
Sodium Thiosulfate 14 g/m2/4 h
2 months
Intra-arterial cisplatin with sodium thiosulfate caused relatively less severe cisplatin ototoxicity than usual intravenous cisplatin chemoradiation.
Not reported
Crabb et al. 2017 RCT 94 Bladder Germ cell Head and neck Lung
200 mg/m2
Audiometry
Aspirin 975 mg three times a day for 4 -5 days
3 months
Aspirin did not protect patients receiving cisplatin. Patients demonstrated mean combined hearing loss of 49 dB vs 36 dB(p=0.233).
Renal toxicity affected more patients in the aspirin arm (17.8% vs 10.2%), the rest of toxicities were similar between arms.
Nasr et al. 2018
Non-randomized clinical trial
Any cancer
Average cumulative cisplatin dose 546.3 ± 111.58 mg
Audiometry
Intra‑tympanic methylprednisolone 40 mg/ml
After cisplatin dose reached 400 mg.
Significant increases in the average pure‐tone thresholds at 6000 Hz were found in both the study and control groups (P = <0.001 and <0.001, respectively) at 6000 and 8000 Hz.
Not reported
Delarestaghi et al. 2018 RCT 79 Lymphoma Gastric
75 mg/m2
Audiometry & otoacoustic emissions
Sertraline 25 - 50 mg/d
3 months
Level of distortion product otoacoustic emissions was unchanged 57.1% and 17.1% in the sertraline and placebo groups, respectively(p=0.000).
11.4% had severe nausea and vomiting in the sertraline group
Rolland et al. 2019 RCT 13
Head and neck
100 mg/m2
Audiometry and Bone conduction audiograms
Transtympanic sodium thiosulfate (dose 0.1 ml).
18 months
The average loss of hearing was 1.3 dB less for treated ears compared to control ears (p = 0.61) 3 and 10 Hz.
3 patients reported dizziness and 1 patient had vertigo. Pain in the middle ear was noted for 4 patients.
Duinkerken et al. 2021 Single-blind placebo controlled study. 12 Lung Head and neck Mesothelioma Thymus carcinoma
75 - 100 mg/m2
Audiometry
Transtympanic Sodium Thiosulfate 0.5% 2.0 ml
3 months
Shift pure-tone average at 8 -12.5 Hz was 18.4 dB less in treated ears compared to untreated ears (p=0.068).
Vertigo, pain and tinnitus
Fernandez et al. 2021 observational study 277
Head and neck
200 mg/m2
Audiometry
Various statins at different doses
3 months
Atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01) (OR = 0.47; 95% CI, 0.30–0.78).
Not reported
Moreno et al. 2022 RCT 23 Lung Bladder Unknown origin
70 -100 mg/m2
Audiometry
Intratympanic dexamethasone 8mg
2 months
Audiometric analysis showed a higher hearing threshold in the study group at frequencies of 500, 1000, and 6000 Hz: 4.9 dB, 5.5 dB, and 16 dB (p < 0.05).
Infections 8.6% and permanent perforation 34.8%.