Neurotoxicity Caused by the Treatment with Platinum Analogues

Abstract

Platinum agents (cisplatin, carboplatin, and oxaliplatin) are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin-induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted.

Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation

“…It is well-known that cisplatin affects calcium homeostasis and its desired and undesired effects involve the change of calcium homeostasis (30). It has been reported that the clinical and side effects of cisplatin could be changed by altering the calcium homeostasis.…”

Ameliorative effect ofApodytes dimidiataon cisplatin-induced nephrotoxicity in Wistar rats

“…Generation of oxidative stress and release of NO are considered to be the prime factors for cisplatin-induced nephrotoxicity (Pan et al 2009). Superoxide (Davis et al 2001), hydrogen peroxide (Kadikoylu et al 2004) and hydroxyl (Shino et al 2003) radicals increased by cisplatin, stimulates lipid peroxidation (Sadzuka et al 1992) and results in the inhibition of antioxidant enzyme activities (Mora et al 2003), which is responsible for nephrotoxicity (Amptoulach & Tsavaris 2011;Naqshbandi et al 2012;Ognjanovic et al 2012). To ameliorate these side effects, complementary agents of high antioxidant potential have been recently investigated (Monti & Yang 2005).…”

Application of liposomal technologies for delivery of platinum analogs in oncology

“…The toxicity to the peripheral nervous system is one of the key dose-limiting toxicities. 10 All three drugs also have relatively short blood circulation times, resulting in suboptimal pharmacokinetics. For cisplatin, nephrotoxicity as well as nausea and vomiting have significantly limited its clinical use.…”