Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

Abstract

Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the case of bortezomib and thalidomide-induced peripheral neuropathy.

EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma

“…However, it is similar to reported levels in adult patients with other CDP-treated cancers, who are more prone to this side effect (24,25). Approximately one-third of patients experienced 1 or more episodes of nephrotoxicity, mostly G1, but in 1 case dialysis was required.…”

Platinum‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…This remarkable variability still needs to be fully explained because different studies have failed to unequivocally indicate which might be the risk factors or the predictors for the final neurological outcome in each patient. Apart from cumulative dose, which is clearly associated with more severe neurotoxicity, several other apparently obvious risk factors for peripheral nerve damage failed to demonstrate consistent results in different studies . This is the case for diabetes, age, previous chemotherapy, while other risk factors less commonly associated to increased incidence of peripheral neuropathies, such as body mass index and smoking, were occasionally reported.…”

Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron

“…Another well‐known chemotherapy‐induced adverse effect is neuropathic pain, which affects limbs in a so‐called “stocking and glove” manner . In contrast, the occurrence of visceral pain related to chemotherapy has received less attention.…”

“…Another well-known chemotherapy-induced adverse effect is neuropathic pain, which affects limbs in a so-called "stocking and glove" manner. 24 In contrast, the occurrence of visceral pain related to chemotherapy has received less attention. Unlike somatic pain, visceral pain is diffuse, difficult to localize, irradiated to superficial structures, and often accompanied by nausea, vomiting, and other manifestations.…”