Various methods have been tested and deployed clinically to identify and minimize
cisplatin ototoxicity. Upon early identification of
hearing loss, one of the possible approaches to reducing future
ototoxicity is to increase the gaps or breaks between cycles or doses of
cisplatin. However, recent findings about the retention of
cisplatin in the cochlea and the potential for its long-term ototoxic effects call into question whether such an approach is effective in reducing
hearing loss. The current study was undertaken to determine whether increasing the rest intervals between cycles of
cisplatin altered the resulting
ototoxicity. CBA/CaJ mice were exposed to a cumulative dose of 48 mg/kg
cisplatin delivered in three cycles of 16 mg/kg (4 mg/kg per day for 4 consecutive days). The cycles were separated by either 10, 17, or 87 days to determine if the inter-cycle rest intervals affected resulting
ototoxicity.
Ototoxicity was measured using auditory brainstem response threshold shifts and hair cell losses. Results indicated that longer intervals between cycles of
cisplatin led to lower threshold shifts and outer hair cell lesions. The results support the principle that 'slowing down'
cisplatin dosing by increasing rest intervals between doses can reduce the ototoxic side effect. Further testing is needed to optimize the timing and to determine the impact of longer inter-cycle intervals on
cisplatin's anti-
tumor efficacy.