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Co-occurrence and metabolic biomarkers of sensory and motor subtypes of peripheral neuropathy from paclitaxel

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Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel.

Methods

Data were from a prospective cohort of 60 patients with breast cancer receiving up to 12 weekly infusions of 80 mg/m2 paclitaxel (NCT02338115). European Organisation for Research and Treatment of Cancer Quality of Life questionnaire CIPN20 was used to evaluate CIPN. Clusters of the time course of sensory (CIPNS), motor (CIPNM), and the difference between sensory and motor (CIPNS–CIPNM) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPNS and CIPNM were investigated using linear regressions adjusted for baseline CIPN, paclitaxel pharmacokinetics, and body mass index.

Results

More sensory than motor CIPN was found (CIPNS change: mean = 10.8, ranged [−3.3, 52.1]; CIPNM change: mean = 3.5, range: [−7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPNS: mean = 12.7 vs. 40.9 vs. 74.3, p < 0.001; maximum CIPNM: mean = 5.4 vs. 25.5 vs. 36.1, p < 0.001; average CIPNS–CIPNM: mean = 2.8 vs. 5.8 vs. 24.9, p < 0.001). Biomarkers of motor CIPN were similar to previously identified biomarkers of sensory CIPN, including lower serum histidine (p = 0.029).

Conclusion

Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients’ outcomes.

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Data availability

The datasets analyzed during the current study are not publicly available due to patient privacy requirements but are available from the corresponding author on reasonable request.

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Funding

This research was funded in part by the National Center for Advancing Translation Sciences (NCATS National Cancer 2UL1TR000433, KL2TR000434) (DLH) and National Cancer Institute (NCI P30CA046592) through use of the UM Pharmacokinetics Core. Dr. Kathleen Stringer’s effort was supported, in part, by a Grant from the National Institute of General Medical Sciences (NIGMS R35 GM136312). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NCATS, NCI, or NIGMS.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Room 3054, Ann Arbor, MI, 48109-1065, USA

    Ciao-Sin Chen, Kathleen A. Stringer & Daniel L. Hertz

  2. University of Alabama at Birmingham School of Nursing, Birmingham, AL, USA

    Ellen M. Lavoie Smith

  3. NMR Metabolomics Laboratory, University of Michigan College of Pharmacy, Ann Arbor, MI, USA

    Kathleen A. Stringer

  4. University of Michigan Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA

    N. Lynn Henry & Daniel L. Hertz

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  1. Ciao-Sin Chen
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  2. Ellen M. Lavoie Smith
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  3. Kathleen A. Stringer
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  4. N. Lynn Henry
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  5. Daniel L. Hertz
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Contributions

All authors contributed to the study conception and design. Data analyses were performed by CSC. The first draft of the manuscript was written by CSC and DLH, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Daniel L. Hertz.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by Institutional Review Boards of the University of Michigan Medical School (IRBMED) (HUM00086259).

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Informed consent was obtained from all individual participants included in the study.

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Chen, CS., Smith, E.M.L., Stringer, K.A. et al. Co-occurrence and metabolic biomarkers of sensory and motor subtypes of peripheral neuropathy from paclitaxel. Breast Cancer Res Treat 194, 551–560 (2022). https://doi.org/10.1007/s10549-022-06652-x

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  • DOI: https://doi.org/10.1007/s10549-022-06652-x

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