Statins Effect on Incidence of Side Effects of Platinum Based Chemotherapy

Ototoxicity, Solid Tumors

platinum based chemotherapy, Cisplatin, adverse effects, ototoxicity, statins

Platinum based chemotherapy (mainly Cisplatin) is known to cause a variety of adverse effects, including Ototoxicity and nephrotoxicity. Ototoxicity is estimated to affect about 36% of adult patients treated with cisplatin, many therapeutic interventions have been studied to reduce the risk of developing ototoxicity from Cisplatin treatment, Statins have been studied in animals and have shown promising results, this study is aimed to explore the effect of statins on the incidence of ototoxicity in humans.

Cisplatin and other platinum salt agents, including carboplatin and oxaliplatin, are widely used chemotherapy agents in patients with solid malignancies. These agents remain the backbone of treatment for ovarian, cervical, testicular, non-small-cell lung, bladder, and head and neck cancers. It is estimated that more than 500,000 patients diagnosed with these cancers annually in the United States could be candidates for treatment with cisplatin. However, adverse effects such as ototoxicity, neurotoxicity, and nephrotoxicity can sometimes limit their use. The incidence of ototoxicity induced by cisplatin has been estimated to be 36% of adult patients with cancer and 40%-60% of pediatric patients. Ototoxicity can be vestibular or cochlear toxicity or both, which can manifest as tinnitus (ringing in the ear), ear pain, and frank hearing loss. The receipt of cisplatin is associated with a 5-fold increase in the risk of hearing impairment, and the incidence and severity are cumulative with exposure. Ototoxicity can manifest as tinnitus, hearing loss in the high-frequency range (4,000 to 8,000 Hz), or at late stages, a decreased ability to hear in the lower-frequency normal conversation range. It can occur during or after treatment and can be unilateral or bilateral affect both ears. Usually, hearing loss can start at higher frequencies in the beginning and can be permanent. In fact, severe ototoxicity with deafness has been reported even after a single cycle of cisplatin. Hence, monitoring and early identification of cisplatin-induced hearing loss are crucial to prevent detrimental impact on hearing and thereby the quality of life (QoL). Children affected by hearing loss have a poorer QoL as evident from their ability to communicate and interact with family and peers, their independence, and emotional well-being.The negative impact of hearing impairment on the patients' health-related QoL including social isolation, anxiety, and depression is well supported by a large body of evidence. In the literature, two studies were found exploring the effect of statins on the incidence of ototoxicity induced by cisplatin, one retrospective study found that patients who used statins concurrently with their cisplatin chemotherapy had a lower incidence of developing ototoxicity, similar results were proven by a study conducted on mice that found that lovastatin protects against development of ototoxicity resulting from cisplatin therapy , a randomized controlled trial exploring the effect of statins on ototoxicity is needed.

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