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%.
|
|