Objective: Ototoxicity is currently the most frequent dose-limiting side effect of cisplatinum chemotherapy. To date, there is no protocol to prevent dose-related ototoxicity, despite its prevalence and predictability. Previous animal studies have found lactate to be effective in the prevention of cisplatinum-induced ototoxicity. The objective of this study was to test the protective benefits of transtympanic Ringer's lactate in the prevention of cisplatinum-induced ototoxicity.
Study Design: A randomized prospective controlled trial was conducted in an animal model.
Setting: Animal care research facilities of The Montreal Children's Hospital Research Institute.
Subjects and Methods: A total of 44 chinchillas were exposed to systemic cisplatinum injected intraperitoneally in divided cycles to reach the targeted cumulative dosage of 16 mg/kg. Ototopical application of Ringer's lactate solution 0.2 mL twice per day during the chemotherapy cycles was performed. Each animal had one experimental (Ringer's) and one control ear. Distortion product otoacoustic emissions (DPOAEs) were collected for a wide range of frequencies (between 1 and 16 kHz), and scanning electron microscopy was performed to evaluate the protective effects of Ringer's lactate.
Results: Ototopical application of Ringer's lactate solution in our established chinchilla animal model did not provide an otoprotective effect as measured by the DPOAE response and electron microscopy.
Conclusion: In our study, the intratympanic application of Ringer's lactate solution through a tympanostomy ventilation tube did not provide an otoprotective effect. Further studies are needed to better assess the otoprotective or ototoxic effects of Ringer's lactate and other antioxidants on animal and human hearing.
Get full access to this article
View all access options for this article.
References
1.
AdamsMKerbyIJRockerIA comparison of the toxicity and efficacy of cisplatin and carboplatin in advanced ovarian cancer. The Swons Gynaecological Cancer Group. Acta Oncol1989; 28:57–60.
2.
SaitoTAranJM.Comparative ototoxicity of cisplatin during acute and chronic treatment. ORL J Otorhinolaryngol Relat Spec1994; 56:315–20.
3.
Lanvers-KaminskyCKrefeldBDinnesenAGContinuous or repeated prolonged cisplatin infusions in children: a prospective study on ototoxicity, platinum concentrations, and standard serum parameters. Pediatr Blood Cancer2006; 47:183–93.
4.
BrockPPritchardJBellmanSOtotoxicity of high-dose cisplatinum in children. Med Pediatr Oncol1988; 16:368–9.
5.
BertoliniPLassalleMMercierGPlatinum compound-related ototoxicity in children: long-term follow-up reveals continuous worsening of hearing loss. J Pediatr Hematol Oncol2004; 26:649–55.
6.
CoradiniPPCiganaLSelistreSGOtotoxicity from cisplatin therapy in childhood cancer. J Pediatr Hematol Oncol2007; 29:355–60.
7.
McAlpineDJohnstoneBM.The ototoxic mechanism of cisplatin. Hear Res1990; 47:191–203.
8.
RybakLPWhitworthCAMukherjeaDMechanisms of cisplatin-induced ototoxicity and prevention. Hear Res2007; 226:157–67.
9.
WangJLadrechSPujolRCaspase inhibitors, but not c-Jun NH2-terminal kinase inhibitor treatment, prevent cisplatin-induced hearing loss. Cancer Res2004; 64:9217–24.
10.
CampbellKCLarsenDLMeechRPGlutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model. J Am Acad Audiol2003; 14:124–33.
11.
EkbornALaurellGJohnstromPD-Methionine and cisplatin ototoxicity in the guinea pig: D-methionine influences cisplatin pharmacokinetics. Hear Res2002; 165:53–61.
12.
KorverKDRybakLPWhitworthCRound window application of D-methionine provides complete cisplatin otoprotection. Otolaryngol Head Neck Surg2002; 126:683–9.
13.
CampbellKCRybakLPMeechRPD-Methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res1996; 102:90–8.
14.
TeranishiMANakashimaT.Effects of trolox, locally applied on round windows, on cisplatin-induced ototoxicity in guinea pigs. Int J Pediatr Otorhinolaryngol2003; 67:133–9.
15.
ChoeWTChinosornvatanaNChangKW.Prevention of cisplatin ototoxicity using transtympanic N-acetylcysteine and lactate. Otol Neurotol2004; 25:910–5.
16.
DanielSJSahmkowSIMunguiaROtotoxicity of triethanol-amine polypeptide (Cerumenex) in the chinchilla. Laryngoscope2008; 118:478–82.
17.
ChoiKESinkuleJASchilskyRLStability of 5-fluorouracil in large volume parenteral solutions containing cisplatin. J Kor Can Assoc1988; 20:47–52.
18.
HarrisonRVMountRJHirakawaH.Total ablation of cochlear hair cells by perilymphatic perfusion with water. Hear Res1997; 110:229–33.
19.
UedaHNakataSHoshinoM.Effects of effusion in the middle ear and perforation of the tympanic membrane on otoacoustic emissions in guinea pigs. Hear Res1998; 122:41–6.
20.
MountRJTakenoSWakeMCarboplatin ototoxicity in the chinchilla: lesions of the vestibular sensory epithelium. Acta Otolayngol Suppl1995; 519:60–5.
