Peripheral neuropathy and cognitive impairment caused by platinum-based chemotherapy

Platinum-based compounds are used in more than 50% of all combination chemotherapeutic treatment schedules. While highly efficacious, these agents are highly neurotoxic and induce damage to neurons in the peripheral and central nervous systems. Peripheral neuropathy is particularly problematic, causing numbness and pain in the hands and feet, however in severe circumstances symptoms can progress up towards the trunk to affect the entire limb. This increases the risk of falls, impairs mobility and severely impacts daily living. Peripheral neuropathy remains without effective intervention, with current strategies largely relying on opioids to manage neuropathic pain. As such, neuropathy is a common driver of dose reductions, delays and even complete cessation of treatment. Neurotoxicity in the central nervous system most typically presents as cognitive impairment, however, isoften accompanied by a range of neuropsychological symptoms including fatigue, anxiety and depression. These, often chronic, symptoms have profound impacts on a patient's capacity to return to work after cancer, and thus is associated with significant economic burden and a profound loss in quality of life. While it is understood how platinum-based drugs damage neurons, the ability of these drugs to access the brain remains unclear, and as such, cognitive impairment and associated psychoneurological symptoms are poorly managed. This chapter provides an overview of the neurotoxic profiles of platinumbased drugs, the aetiology of both peripheral neuropathy and cognitive impairment, a summary of their risk factors, assessment tools and current evidence on emerging strategies to prevent or manage these symptoms.