N-acetylcysteine
Three randomized placebo-controlled trials have explored if
N-acetylcysteine can avert CiO administered intratympanic(Riga et al.,
2013, Yoo et al., 2014) or orally (Yıldırım et al., 2010). A RCT used
intratympanic N-acetylcysteine at 10% in 20 patients with different
types of tumors. They found that treated ears with N-acetylcysteine had
no significant changes in auditory thresholds while the control ears had
a significant decrease in auditory thresholds at the 8000 Hz frequency
band (P = 0.008) with cisplatin (Riga et al., 2013). Another RCT
assessed the effectiveness of intratympanic N-acetylcysteine at 2% to
prevent hearing and tinnitus due to cisplatin in 11 patients with head
and neck cancer receiving concomitant radiotherapy. No benefit in
hearing preservation or tinnitus incidence was found (Yoo et al. 2014).
The concentration difference of N-acetylcysteine may have influenced the
disparity of the results as the occurrence of side effects. For
instance, the highest concentration of N-acetylcysteine was associated
with pain application among almost all patients (Riga et al., 2013),
while the trial with a lower concentration of N-acetylcysteine did not
report adverse reactions (Yoo et al., 2014). The third RCT compared the
protective hearing effect of placebo, oral N-acetylcysteine, and
salicylate in 54 patients with solid organ tumors receiving cisplatin.
Audiometry and auditory brainstem parameters showed no significant
difference between placebo and salicylate. On the other hand, the
N-acetylcysteine group did have a reduction in cisplatin hearing
ototoxicity at 10,000 and 12,000 Hz (p<0.005) compared to
placebo. Nonetheless, safety outcomes between study interventions were
not reported (Yıldırım et al., 2010).