Oxaliplatin-induced peripheral nerve injury in real-world clinical practice

Cancer is a public health problem and the leading cause of death for patients worldwide. In 2018, about 18 million new cases of cancer and 9.6 million deaths were registered in the world. Platinum-based drugs, as the main drugs in chemotherapy for cancer patients, are widely used in the treatment of various malignant tumors. Oxaliplatin is a third-generation cytotoxic platinum compound, widely utilized in the treatment of various oncological diseases. It is known that the main spectrum of adverse reactions (AR) of oxaliplatin includes neuro- and hematotoxicity, toxic manifestations from the gastrointestinal tract, and hypersensitivity reactions. The most significant manifestation of oxaliplatin neurotoxicity is peripheral nerve damage, the frequency of which accounts for ≥10%, according to the results of safety assessment in clinical trials [1–4] and meta-analyses [5]. There are two forms of neurotoxicity: acute and chronic. Acute neurotoxicity occurs in more than 90% of patients, may debut even during drug infusion, and usually spontaneously resolves in a short time. Chronic neurotoxicity is cumulative, and it is more often observed in patients who received oxaliplatin in a course dose of >540 mg/m2. Despite the sensory nature of neuropathy, it can lead to impairment of physical functions and significantly reduce the quality of life of patients. The safety of oxaliplatin in the Russian Federation has been assessed only in the framework of clinical trials with a small number of participants (less than 100 subjects in each) [7,8]; large-scale clinical trials have not been conducted. Spontaneous reports (SRs) of ADRs are one of the effective systems for assessing the current safety status of drugs without time and sample size restrictions. In addition, analysis of the spectrum of ADRs in SRs can allow assessing the effectiveness of routine measures to prevent the risks of pharmacotherapy, which, in relation to oxaliplatin, includes peripheral nerves injury.