Exploring clinical markers of Axon degeneration processes in Chemotherapy-induced peripheral neuropathy among young adults receiving vincristine or paclitaxel

Approximately 70% of patients receiving neurotoxic chemotherapy (e.g., paclitaxel or vincristine) will develop chemotherapy-induced peripheral neuropathy. Despite the known negative effects of CIPN on physical functioning and chemotherapy dosing, little is known about how to prevent CIPN. The develo...

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Published in:BMC neurology 2024-09, Vol.24 (1), p.366-11, Article 366
Main Authors: Knoerl, Robert, Mazzola, Emanuele, Pazyra-Murphy, Maria, Ryback, Birgitta, Frazier, A Lindsay, Freeman, Roy L, Hammer, Marilyn, LaCasce, Ann, Ligibel, Jennifer, Luskin, Marlise R, Berry, Donna L, Segal, Rosalind A
Format: Article
Language:English
Subjects:
Adolescent
Adult
Alcohol use
Antineoplastic Agents, Phytogenic - adverse effects
Axons - drug effects
Axons - pathology
Biological markers
Biomarkers - blood
Breast cancer
Cancer
Cancer therapies
Chemotherapy
Chemotherapy-induced peripheral neuropathy
Chromatography
Complications and side effects
Cyclic ADP-ribose
Degeneration
Development and progression
Diagnosis
Drug therapy
Female
Gas flow
Humans
Laboratories
Leukemia
Longitudinal Studies
Lymphoma
Male
Mass spectroscopy
NAD
NAD - blood
NAD - metabolism
NAD, human [Supplementary Concept]
Neoplasms
Nerve Degeneration - blood
Nerve Degeneration - chemically induced
Nerve Degeneration - pathology
Nervous system
Neurological research
Neurotoxicity
Paclitaxel
Paclitaxel - adverse effects
Peripheral Nervous System Diseases - blood
Peripheral Nervous System Diseases - chemically induced
Peripheral neuropathy
Plasma
Polyneuropathies
Regression analysis
Risk factors
Self report
Statistical analysis
Vincristine
Vincristine - adverse effects
Young Adult
Young adults
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Summary:Approximately 70% of patients receiving neurotoxic chemotherapy (e.g., paclitaxel or vincristine) will develop chemotherapy-induced peripheral neuropathy. Despite the known negative effects of CIPN on physical functioning and chemotherapy dosing, little is known about how to prevent CIPN. The development of efficacious CIPN prevention interventions is hindered by the lack of knowledge surrounding CIPN mechanisms. Nicotinamide adenine dinucleotide (NAD ) and cyclic-adenosine diphosphate ribose (cADPR) are potential markers of axon degeneration following neurotoxic chemotherapy, however, such markers have been exclusively measured in preclinical models of chemotherapy-induced peripheral neuropathy (CIPN). The overall objective of this longitudinal, observational study was to determine the association between plasma NAD , cADPR, and ADPR with CIPN severity in young adults receiving vincristine or paclitaxel. Young adults (18-39 years old) beginning vincristine or paclitaxel were recruited from Dana-Farber Cancer Institute. Young adults completed the QLQ-CIPN20 sensory and motor subscales and provided a blood sample prior to starting chemotherapy (T1) and at increasing cumulative vincristine (T2: 3-5 mg, T3: 7-9 mg) and paclitaxel (T2: 300-500 mg/m , T3: 700-900 mg/m ) dosages. NAD , cADPR, and ADPR were quantified from plasma using mass spectrometry. Metabolite levels and QLQ-CIPN20 scores over time were compared using mixed-effects linear regression models and/or paired two-sample tests. Participants (N = 50) were mainly female (88%), white (80%), and receiving paclitaxel (78%). Sensory and motor CIPN severity increased from T1-T3 (p 
ISSN:1471-2377
1471-2377
DOI:10.1186/s12883-024-03877-9