Vinca alkaloids, thalidomide and eribulin‐induced peripheral neurotoxicity: From pathogenesis to treatment

Abstract

Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy-induced peripheral neurotoxicity (CIPN) emerged as their main non-hematological and among dose-limiting adverse events. It is generally perceived that vinca alkaloids and the antiangiogenic agent thalidomide are more neurotoxic, compared to eribulin. The exposure to these chemotherapeutic agents is associated with an axonal, length-dependent, sensory polyneuropathy of mild to moderate severity, whereas it is considered that the peripheral nerve damage, unless severe, usually resolves soon after treatment discontinuation. Advanced age, high initial and prolonged dosing, coadministration of other neurotoxic chemotherapeutic agents and pre-existing neuropathy are the common risk factors. Pharmacogenetic biomarkers might be used to define patients at increased susceptibility of CIPN. Currently, there is no established therapy for CIPN prevention or treatment; symptomatic treatment for neuropathic pain and dose reduction or withdrawal in severe cases is considered, at the cost of reduced cancer therapeutic efficacy. This review critically examines the pathogenesis, epidemiology, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of CIPN as a result of exposure to vinca alkaloids, thalidomide and its analogue lenalidomide as also eribulin. K E Y W O R D S assessment, eribulin, peripheral neurotoxicity, thalidomide, vinca alkaloids

Comparing neuropathy in multiple myeloma and AL amyloidosis

“…We had a slight modification, as we substituted the motor NCS of a peroneal nerve with the tibial nerve to avoid a floor-effect in this cohort of mature patients with a suspected moderate PN. The TNS scores were graded as suggesting a minor (1-7), moderate (8)(9)(10)(11)(12)(13)(14) or severe (above 14) PN.…”

The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects

“…Hydroalcoholic extracts were obtained from the leaves of Vinca species, which are known as medicinal plants and having a high content of alkaloids, flavonoids, and phenolic compounds, and well-documented antibacterial, antioxidant, and cytotoxic effects [46][47][48]. The chemical composition of plant extracts is dependent on the plant species, organ and tissue used, harvesting period, environmental conditions, extraction method, and solvent used for preparation [33,49,50].…”

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment

“…It has been recognized that vincristine can influence the movement of Ca 2+ across the mitochondrial membrane, reducing both the quantity and the rate of Ca 2+ absorption and decreasing its efflux [ 31 ]. The modification of the mitochondrial absorption and concentration of Ca 2+ alters the mitochondrial function [ 32 ], with consequently increased exocytosis of neurotransmitters [ 33 ] and release of ROS [ 26 ]. These changes lead to reduced neuronal excitability and glial function, activating apoptosis.…”