Neurological Complications of Conventional and Novel Anticancer Treatments

Alberti, Paola; Salvalaggio, Alessandro; Argyriou, Andreas A.; Bruna, Jordi; Visentin, Andrea; Cavaletti, Guido; Briani, Chiara

doi:10.3390/cancers14246088

Cited by 14 publications

(18 citation statements)

References 202 publications

(244 reference statements)

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“…We also explored if Immune Checkpoint Inhibitors and antibody‐drug conjugates 57 could be considered at increased risk in CMT patients, but no reports suggesting worsening of peripheral neuropathy in these patients were found.…”

Section: Resultsmentioning

confidence: 99%

“…The definite neurotoxic drugs have a well-established clinical phenotype and course, although the severity of PNS damage can be markedly different among treated patients. The strongest evidence for the wide range of severity can be seen in anticancer drug-treated patients, 57,58 representing the largest cohort of subjects exposed to the risk of severe drug-related peripheral neurotoxicity. In this population, it has been firmly demonstrated that the same treatment schedule administered to patients with similar demographic and oncological features could result in negligible peripheral neurotoxicity up to severely disabling and long-lasting PNS damage.…”

Section: Discussionmentioning

confidence: 99%

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Toxic medications in Charcot–Marie–Tooth patients: A systematic review

Cavaletti

Forsey

Alberti

2023

J Peripheral Nervous Sys

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Background and AimsSeveral widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot–Marie–Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence‐based updated recommendations on this clinically relevant topic.MethodsA systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.ResultsThe results of our systematic review provide evidence‐based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug‐related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.InterpretationIt is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non‐oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Toxic medications in Charcot–Marie–Tooth patients: A systematic review

Cavaletti

Forsey

Alberti

2023

J Peripheral Nervous Sys

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“…7 The initial clinical examination should include also the contralateral upper extremity to rule out CIPN, which typically occurs bilaterally as a result of systemic treatment (eg, taxanes or vinca alkaloids). 16 Based on my own clinical experience, neither patients nor their health care providers, even medical oncologists in some cases, tend to associate these unusual neurological symptoms with cancer treatments received as long as 20 years before. In addition, former breast cancer patients often fail to link these sensory-motor symptoms with radiotherapy occurring often decades before.…”

Section: Clinical Characteristics Of Radiation-induced Brachial Plexo...mentioning

confidence: 99%

“…The initial clinical examination should include also the contralateral upper extremity to rule out CIPN, which typically occurs bilaterally as a result of systemic treatment (eg, taxanes or vinca alkaloids) 16 …”

Section: Literature Reviewmentioning

confidence: 99%

Brachial plexopathy after breast cancer: A persistent late effect of radiotherapy

Harris

2023

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Radiation‐induced brachial plexopathy (RIBP) is an iatrogenic, progressively disabling, and often very late effect of adjuvant radiotherapy most commonly seen in breast cancer survivors but also in those treated for lymphoma, lung, and head and neck cancers. In late‐onset RIBP following breast cancer, the nerve injury is chronic and irreversible, occurring more commonly when axillary and/or supraclavicular nodes have been irradiated, as well as the breast/chest wall. RIBP is manifested initially by paresthesia, hypoesthesia, dysesthesia, and later by weakness in the ipsilateral hand with those symptoms progressing distally to proximally up through the shoulder. Depressed/absent deep tendon reflexes in the upper extremity and muscle fasciculations occur also. Neither patients nor their health care providers tend to associate these unusual neurological symptoms with cancer treatments received ≥20 years prior, often failing to link these sensory‐motor symptoms with radiotherapy decades before. Because long‐term follow‐up of these patients now typically falls to general practitioners, many cases may be missed or misdiagnosed because of the rarity of this disorder. Physiatrists and allied rehabilitation professionals must be aware of this progressively disabling, incurable condition to provide appropriate diagnoses and compensatory rehabilitation therapies. Additionally, professional oncology organizations should include RIBP in their long‐term, survivorship guidelines for breast cancer. Researchers examining the iatrogenic late effects of radiotherapy should extend their follow‐up periods well beyond the current 5–6 years to ascertain the true incidence of RIBP today. Rehabilitation providers must continue to advocate for awareness, diagnosis, and management of iatrogenic outcomes experienced by long‐term cancer survivors.

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“…Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common and potentially long-term/persistent adverse event of the most commonly used anticancer drugs: platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors and thalidomide. 7 There is no state of the art efficacious curative and/or preventive treatment for this condition. 19,22,31,38 In part, this unmet clinical and scientific need is due to an incomplete understanding of axonal damage mechanisms related to different anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Morphofunctional characterisation of axonal damage in different rat models of chemotherapy‐induced peripheral neurotoxicity: The role of nerve excitability testing

Chiorazzi,

Canta,

Carozzi

et al. 2023

J Peripheral Nervous Sys

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Background and AimsChemotherapy‐induced peripheral neurotoxicity (CIPN) is a common and long‐lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench to bedside. Nerve excitability testing (NET) enables to test in vivo axonal properties and can be used to monitor early changes leading to axonal damage.MethodsWe tested NET use in two different CIPN rat models: oxaliplatin (OHP) and paclitaxel (PTX). Animals (female) were chronically treated with either PTX or OHP and compared to respective control animals. NET was performed as soon as the first injection was administered. At the end of the treatment, CIPN onset was verified via a multimodal and robust approach: nerve conduction studies, nerve morphometry, behavioural tests and intraepidermal nerve fibre density.ResultsNET showed the typical pattern of axonal hyperexcitability in the 72 h following the first OHP administration, whereas it showed precocious signs of axonal damage in PTX animals. At the end of the month of treatment, OHP animals showed a pattern compatible with a mild axonal sensory polyneuropathy. Instead, PTX cohort was characterised by a rather severe sensory axonal polyneuropathy with minor signs of motor involvement.InterpretationNET after the first administration demonstrated the ongoing OHP‐related channelopathy, whereas in PTX cohort it showed precocious signs of axonal damage. Therefore, NET could be suggested as an early surrogate marker in clinical trials, to detect precocious changes leading to axonal damage.

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Neurological Complications of Conventional and Novel Anticancer Treatments

Cited by 14 publications

References 202 publications

Toxic medications in Charcot–Marie–Tooth patients: A systematic review

Toxic medications in Charcot–Marie–Tooth patients: A systematic review

Brachial plexopathy after breast cancer: A persistent late effect of radiotherapy

Morphofunctional characterisation of axonal damage in different rat models of chemotherapy‐induced peripheral neurotoxicity: The role of nerve excitability testing

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