Dataset Information

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

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 (CIPN_S), motor (CIPN_M), and the difference between sensory and motor (CIPN_S-CIPN_M) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPN_S and CIPN_M were investigated using linear regressions adjusted for baseline CIPN, paclitaxel pharmacokinetics, and body mass index.

Results

More sensory than motor CIPN was found (CIPN_S change: mean = 10.8, ranged [-3.3, 52.1]; CIPN_M change: mean = 3.5, range: [-7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPN_S: mean = 12.7 vs. 40.9 vs. 74.3, p < 0.001; maximum CIPN_M: mean = 5.4 vs. 25.5 vs. 36.1, p < 0.001; average CIPN_S-CIPN_M: 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.

SUBMITTER: Chen CS

PROVIDER: S-EPMC9310087 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Chen Ciao-Sin CS Smith Ellen M Lavoie EML Stringer Kathleen A KA Henry N Lynn NL Hertz Daniel L DL

Breast cancer research and treatment 20220628 3

<h4>Purpose</h4>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.<h4>Methods</h4>Data ...[more]

PMID: 35760975

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Project description:Introduction: We conducted a randomized controlled trial evaluating the efficacy and tolerability of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with early breast cancer receiving neo/adjuvant weekly paclitaxel. Methods: Patients were recruited from the National Cancer Centre Singapore and randomized (1:1) to receive either cryotherapy or usual care. Cryotherapy was applied as frozen gloves and socks on all extremities from 15 min before paclitaxel until 15 min post-infusion every cycle. Efficacy was measured by patient-reported outcomes (Patient Neurotoxicity Questionnaire [PNQ] and EORTC QLQ-CIPN20) and electrophysiological assessments. The primary endpoint was PNQ severity at 2 weeks after 12 cycles of weekly paclitaxel. Results: A total of 46 patients were recruited, of which 8 dropped out before paclitaxel treatment, leaving 38 evaluable. There was no significant difference in PNQ severity between cryotherapy and usual care at 2 weeks after paclitaxel treatment (sensory: p = 0.721; motor: p = 1.000). A benefit was observed at 3 months post-paclitaxel based on PNQ (sensory: 14.3 vs. 41.2%, p = 0.078; motor: 0 vs. 29.4%, p = 0.012) and CIPN20 (sensory: β = -3.6, 95%CI = -10.5-3.4, p = 0.308; motor: β = -7.3, 95%CI = -14.6-0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (β = -5.84, 95%CI = -11.15 to -0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (β = 0.544, 95%CI = 0.108-0.98, p = 0.014), suggesting possible autonomic benefits from cryotherapy. Temporary interruption with cryotherapy occurred in 80.9% of the subjects due to cold intolerance. Conclusions: There is insufficient evidence that cryotherapy prevents sensory neuropathy which may be due to the high rates of cryotherapy interruption in this study. The autonomic benefits of cryotherapy should be further investigated with appropriate outcome measures. Clinical Trial Registration: ClinicalTrials.gov: NCT03429972.

Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

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