Cisplatin is a potent chemotherapy drug widely used in cancer treatment. While effective against various malignancies, it causes significant side effects, including permanent hearing loss. Understanding this complication is important for patients and families navigating cancer therapy.
Understanding Cisplatin
Cisplatin is a platinum-based chemotherapeutic agent. Approved by the FDA in 1978, it has been a mainstay in treating various adult cancers, such as bladder, lung, and ovarian cancers, and is also used in pediatric cancers.
Cisplatin’s effectiveness stems from its ability to interfere with cancer cell DNA. Once inside a cell, its chloride ligands are replaced by water molecules, activating the drug. This activated form then binds to DNA, forming cross-links. These DNA cross-links distort the double helix, blocking DNA replication and transcription, processes cancer cells rely on. This DNA damage triggers programmed cell death, or apoptosis.
How Cisplatin Causes Hearing Loss
Cisplatin-induced hearing loss, also known as ototoxicity, results from the drug’s damaging effects on the inner ear, specifically the cochlea. Cisplatin enters cochlear cells through various transporters, and once inside, it can remain for months to years. This prolonged retention contributes to the drug’s damaging effects.
The drug causes harm through multiple mechanisms, leading to the death of cochlear cells. It can directly damage both mitochondrial and nuclear DNA. This DNA damage, along with the inhibition of protein synthesis, triggers the activation of apoptotic pathways.
Cisplatin also generates reactive oxygen species (ROS), causing oxidative stress and inflammation within the cochlea. This oxidative damage further contributes to the death of outer hair cells, which are specialized sensory cells in the cochlea responsible for amplifying sound. The loss of these outer hair cells leads to permanent sensorineural hearing loss, often primarily affecting high frequencies.
Who is Affected and Risk Factors
Cisplatin-induced hearing loss is a common side effect, affecting a significant portion of patients. In adults, the incidence ranges from 23% to 50%. Children are particularly susceptible, with reported rates of permanent sensorineural hearing loss ranging from 50% to 70% in those receiving cisplatin chemotherapy.
Several factors increase the likelihood and severity of hearing loss. A higher cumulative cisplatin dose is a consistent risk factor. Younger age at treatment is also strongly associated with more severe ototoxicity, with children under 5 years old experiencing the highest prevalence of moderate to severe hearing loss, often exceeding 50%. Concurrent treatments, such as vincristine or carboplatin, can also increase risk. Pre-existing hearing conditions or concurrent cranial irradiation can also increase susceptibility.
Detection and Management Strategies
Cisplatin-induced hearing loss often manifests as tinnitus, a ringing in the ears, and a decrease in the ability to hear high-frequency sounds. With continued therapy, the hearing loss can progress to lower frequencies important for conversational speech. This hearing loss is typically bilateral and permanent.
Detection of cisplatin-induced hearing loss relies on audiological assessments performed before, during, and after treatment. Ototoxicity monitoring programs utilize a combination of behavioral and objective tests. High-frequency audiometry and otoacoustic emissions (OAEs) are important for early detection, as they can identify cochlear injury before a patient subjectively notices hearing loss.
While no universally approved treatments exist for preventing or reversing cisplatin-induced hearing loss in adults, sodium thiosulfate (Pedmark) received FDA approval in 2022 for reducing the risk of ototoxicity in pediatric patients with solid tumors. This agent works by binding to and inactivating cisplatin, and by influencing antioxidant enzymes within cochlear cells. It is administered as an intravenous infusion after cisplatin to avoid interfering with the chemotherapy’s anti-tumor effects. Other strategies under investigation include localized drug delivery methods, such as intratympanic injections, and the use of antioxidants or statins, which have shown some protective effects in studies.