Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients

Abstract

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mechanisms, as most existing information stems from studies in animal models or adult cancer patients. Herein, we aim to provide an understanding of CIPN in the pediatric population and focus on the 6 main substance groups that frequently cause CIPN, namely the vinca alkaloids (vincristine), platinum-based antineoplastics (cisplatin, carboplatin and oxaliplatin), taxanes (paclitaxel and docetaxel), epothilones (ixabepilone), proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). We discuss the clinical manifestations, assessments and diagnostic tools, as well as risk factors, pathophysiological processes and current pharmacological and non-pharmacological approaches for the prevention and treatment of CIPN.

Targeting translation: A review of preclinical animal models in the development of treatments for chemotherapy‐induced peripheral neuropathy

“…Furthermore, very few CIPN preclinical studies concentrate on paediatric populations (rodents <6 weeks of age) 62 to examine the effects of neurotoxic chemotherapy in the developing nervous system. 64,65 In addition, few preclinical studies have incorporated tumourbearing mice when investigating CIPN, despite some evidence suggesting that the presence of a tumour may affect neuropathic symptoms. 29,66 Malignancies can also cause significant inflammation, which is postulated as an important contributor to CIPN.…”

“…However, the majority of CIPN studies are performed on mice with an age equivalence to young adult humans (mice that are 6–14 weeks old). Furthermore, very few CIPN preclinical studies concentrate on paediatric populations (rodents <6 weeks of age) 62 to examine the effects of neurotoxic chemotherapy in the developing nervous system 64,65 …”

Protective effect of oxytocin on vincristine-induced gastrointestinal dysmotility in mice

“…In addition to the direct damage of the nervous system, characterized by VCR-induced peripheral neuropathy, the pathological mechanisms of VCR-induced neurotoxicity are also related to changes in ion channel activity, oxidative stress, and inflammation ( Tay et al, 2022 ). VCR treatment leads to oxidative stress in the nervous system, including the sciatic nerve, spinal cord, and brain ( Chen et al, 2020 ; Khan et al, 2021 ).…”

Results of evaluation of neurometabolic and rehabilitation therapy for vincristine polyneuropathy in children with acute lymphoblastic leukemia

“…Основным противоопухолевым препаратом, входящим в протоколы лечения ОЛЛ у детей, является винкристин. К распространённым побочным эффектам цитостатика относится полиневропатия, её частота встречаемости может достигать 80 % и более [6,7]. Винкристиновая полиневропатия (ВП) сопровождается нарушением двигательных, чувстви-тельных и вегетативных функций, что приводит к развитию изнурительных симптомов, сохраняющихся в течение нескольких месяцев или даже лет после прекращения лечения [8].…”

“…Одна из сложных задач заключается в лечении ВП и в настоящее время эффективных терапевтических стратегий не разработано, поскольку патогенетические закономерности до конца не изучены. Существующие гипотезы, лежащие в основе механизмов развития ВП многочисленны, и включают прямое повреждение аксонов, митохондриальную дисрегуляцию, а также участие факторов роста и цитокинов [7,8]. Например, в одном из пилотных исследований продемонстрирована корреляция между тяжестью невропатии, вызванной химиотерапией, и дефицитом фактора роста нервов [18].…”