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BMC Cancer Nov 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory... (Clinical Trial)
Clinical Trial
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a painful, dose-limiting adverse effect of commonly used chemotherapeutic agents. The purpose of this exploratory study was to evaluate the efficacy and safety of mirogabalin in patients with moderate to severe CIPN during chemotherapy and the effects of 12 weeks' intervention on chemotherapy completion and CIPN severity.
METHODS
Patients experiencing moderate to severe CIPN while undergoing oxaliplatin- or taxane-containing chemotherapy for colorectal, gastric, non-small-cell lung, or breast cancer received mirogabalin at between 5 and 15 mg twice daily. The primary endpoint was change in numeric rating scale (NRS) score for pain from baseline to week 12. Secondary endpoints included NRS scores for tingling and sleep, completion of chemotherapy, severity of CIPN, and quality of life (QOL) scores. The safety endpoint was incidence of adverse events.
RESULTS
Of 58 patients who consented to participation, 52 were eligible and constituted the full analysis set and safety analysis set. From baseline to week 12 (last observation carried forward [LOCF]), NRS score decreased by 30.9%: mean change (95% confidence interval [CI]), - 1.7 (- 2.4 to - 1.0) (p < 0.001). Patients with baseline NRS of ≥ 6 experienced a 44.0% reduction in score from baseline to week 12 (LOCF): mean change (95% CI), - 3.3 (- 5.0 to - 1.5) (p = 0.002). Chemotherapy was discontinued in 18 (34.6%) patients; CIPN led to discontinuation in only 2 (3.8%). There was no notable worsening of CIPN severity in terms of Common Terminology Criteria for Adverse Events grade or Modified Total Neuropathy Score-reduced, although use of pain medications during chemotherapy might cause worsening of CIPN due to underestimation of subjective symptoms. QOL score based on the EuroQol five-dimensional descriptive system did not worsen during the 12 weeks. Thirty-one percent of patients experienced adverse drug reactions, and the most common event was somnolence (13.5%). Serious adverse events and death occurred in 3 patients and 1 patient, respectively; however, they were unrelated to mirogabalin treatment.
CONCLUSIONS
Intervention with mirogabalin during chemotherapy may be effective and safe for cancer patients with moderate to severe CIPN. It can contribute to completion of chemotherapy without worsening of CIPN.
TRIAL REGISTRATION
Japan Registry of Clinical Trials (jRCTs031210101, registered 20/5/2021).
Topics: Humans; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pain; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life
PubMed: 37951905
DOI: 10.1186/s12885-023-11560-4 -
Experimental Neurology Feb 2020Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor... (Review)
Review
Paclitaxel (Brand name Taxol) is widely used in the treatment of common cancers like breast, ovarian and lung cancer. Although highly effective in blocking tumor progression, paclitaxel also causes peripheral neuropathy as a side effect in 60-70% of chemotherapy patients. Recent efforts by numerous labs have aimed at defining the underlying mechanisms of paclitaxel-induced peripheral neuropathy (PIPN). In vitro models using rodent dorsal root ganglion neurons, human induced pluripotent stem cells, and rodent in vivo models have revealed a number of molecular pathways affected by paclitaxel within axons of sensory neurons and within other cell types, such as the immune system and peripheral glia, as well skin. These studies revealed that paclitaxel induces altered calcium signaling, neuropeptide and growth factor release, mitochondrial damage and reactive oxygen species formation, and can activate ion channels that mediate responses to extracellular cues. Recent studies also suggest a role for the matrix-metalloproteinase 13 (MMP-13) in mediating neuropathy. These diverse changes may be secondary to paclitaxel-induced microtubule transport impairment. Human genetic studies, although still limited, also highlight the involvement of cytoskeletal changes in PIPN. Newly identified molecular targets resulting from these studies could provide the basis for the development of therapies with which to either prevent or reverse paclitaxel-induced peripheral neuropathy in chemotherapy patients.
Topics: Animals; Antineoplastic Agents, Phytogenic; Humans; Mice; Paclitaxel; Peripheral Nervous System Diseases; Rats; Rodentia
PubMed: 31758983
DOI: 10.1016/j.expneurol.2019.113121 -
PloS One 2019Diabetic peripheral neuropathy (DPN), the most common chronic complication of diabetes, has become an important public health crisis worldwide. Given that DPN is... (Meta-Analysis)
Meta-Analysis
Diabetic peripheral neuropathy (DPN), the most common chronic complication of diabetes, has become an important public health crisis worldwide. Given that DPN is extremely difficult to treat, determining its risk factors and controlling it at an early stage is critical to preventing its serious consequences and the burden of social disease. Current studies suggest that the risk factors for diabetic peripheral neuropathy are the duration of diabetes, age, glycosylated hemoglobin A1c (HbA1c), diabetic retinopathy (DR), smoking, and body mass Index (BMI). However, most of the aforementioned studies are cross-sectional, and the sample sizes are very limited, so the strength of causal reasoning is relatively low. The current study systematically evaluated DPN's influencing factors in patients with type 2 diabetes using evidence-based medicine. Overall, 16 included studies (14 cross-sectional studies and 2 case-control studies including 12,116 cases) that conformed to the present criteria were included in the final analysis. The results suggested that the duration of diabetes (MD 2.5, 95% CI 1.71~3.29), age (MD 4.00, 95% CI 3.05~4.95), HbA1c (MD 0.48, 95% CI 0.33~0.64), and DR (OR 2.34, 95% CI 1.74~3.16) are associated with significantly increased risks of DPN among diabetic patients, while BMI, smoking, total triglyceride (TG), and total cholesterol (TC) did not indicate any risks of increasing DPN. The findings provide a scientific basis for a further understanding of the causes of type 2 diabetes complicated with peripheral neuropathy and the improvement of preventive strategies. The next step is to conduct further high-quality prospective cohort studies to validate this paper's findings.
Topics: Age Factors; Diabetic Neuropathies; Glycated Hemoglobin; Humans; Peripheral Nervous System Diseases; Risk Factors
PubMed: 30785930
DOI: 10.1371/journal.pone.0212574 -
Cancer Oct 2022To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients.
METHODS
In this prospective, pragmatic, and patient-preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice-weekly acupuncture-only (group A) or acupuncture with additional manual-movement or mind-body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool. Other QoL-related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well-being questionnaire. Von Frey measurements examined perception thresholds.
RESULTS
Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline-to-6-week assessment scores improved significantly in the intervention arm (vs controls) on FACT-Tax (p = .038) and emotional well-being (p = .04) scores; FACT-TAX scores for hand numbness/tingling (p = .007) and discomfort (p < .0001); and EORTC physical functioning (p = .045). Intervention groups A and B showed improved FACT-Tax physical well-being (p < .001), FACT-TAX total score (p < .001), FACT-TAX feet discomfort (p = .003), and EORTC pain (p = .017) scores.
CONCLUSIONS
Acupuncture, with or without CIM modalities, can relieve CIPN-related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.
Topics: Acupuncture Therapy; Antineoplastic Agents; Humans; Hypesthesia; Neoplasms; Pain; Peripheral Nervous System Diseases; Prospective Studies; Quality of Life; Taxoids
PubMed: 35960141
DOI: 10.1002/cncr.34422 -
Medical Sciences (Basel, Switzerland) Jan 2023Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in... (Review)
Review
Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN) with Non-Pharmacological Interventions: Clinical Recommendations from a Systematic Scoping Review and an Expert Consensus Process.
Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind-body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs.
Topics: Humans; Antineoplastic Agents; Consensus; Peripheral Nervous System Diseases; Neoplasms; Complementary Therapies
PubMed: 36810482
DOI: 10.3390/medsci11010015 -
The Oncologist Apr 2020Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population.
PATIENTS AND METHODS
Women with stage I-III breast cancer with grade 1 or higher CIPN after taxane-containing adjuvant chemotherapy were randomized 1:1 to an immediate acupuncture (IA) arm or to a waitlist control group (CG). Participants in the IA arm received 18 sessions of acupuncture over 8 weeks, then received no additional acupuncture. Patients in the CG arm received usual care over 8 weeks, followed by nine sessions of acupuncture over 8 weeks. Measures including Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy-Neurotoxicity subscale (FACT-NTX), and Brief Pain Inventory-short form (BPI-SF) were collected at baseline and at 4, 8, and 16 weeks after enrollment.
RESULTS
Forty women (median age, 54) were enrolled (20 to IA and 20 to CG), with median time between completion of chemotherapy and enrollment of 14 months (range 1-92). At 8 weeks, participants in the IA arm experienced significant improvements in PNQ sensory score (-1.0 ± 0.9 vs. -0.3 ± 0.6; p = .01), FACT-NTX summary score (8.7 ± 8.9 vs. 1.2 ± 5.4; p = .002), and BPI-SF pain severity score (-1.1 ± 1.7 vs. 0.3 ± 1.5; p = .03), compared with those in the CG arm. No serious side effects were observed.
CONCLUSION
Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings.
IMPLICATIONS FOR PRACTICE
Chemotherapy-induced peripheral neuropathy (CIPN) is a toxicity that often persists for months to years after the completion of adjuvant chemotherapy for early breast cancer. In a randomized pilot trial of 40 breast cancer survivors with CIPN, an 8-week acupuncture intervention (vs. usual care) led to a statistically and clinically significant improvement in subjective sensory symptoms including neuropathic pain and paresthesia. Given the lack of effective therapies and established safety profile of acupuncture, clinicians may consider acupuncture as a treatment option for mild to moderate CIPN in practice.
Topics: Acupuncture Therapy; Antineoplastic Agents; Breast Neoplasms; Cancer Survivors; Child; Child, Preschool; Female; Humans; Infant; Peripheral Nervous System Diseases; Pilot Projects
PubMed: 32297442
DOI: 10.1634/theoncologist.2019-0489 -
EBioMedicine Apr 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role...
BACKGROUND
Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment.
METHODS
The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs.
FINDINGS
The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice.
INTERPRETATION
In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN.
FUNDING
This study was funded by the National Natural Science Foundation of China81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu ProvinceBK20191253; Major Project of "Science and Technology Innovation Fund" of Nanjing Medical University2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu ProvinceBE2019732; Nanjing Special Fund for Health Science and Technology DevelopmentYKK19170.
Topics: Mice; Animals; Extracellular Traps; Peripheral Nervous System Diseases; Oxaliplatin; Hyperalgesia; Antineoplastic Agents
PubMed: 36870200
DOI: 10.1016/j.ebiom.2023.104499 -
Cells Jun 2020Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired... (Review)
Review
Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature-deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for "peripheral amyloid neuropathies".
Topics: Amyloidogenic Proteins; Humans; Peripheral Nervous System Diseases
PubMed: 32604774
DOI: 10.3390/cells9061553 -
Basic & Clinical Pharmacology &... Aug 2014Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral... (Review)
Review
Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated with DIPN.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Optic Nerve Diseases; Peripheral Nerves; Peripheral Nervous System Diseases
PubMed: 24786912
DOI: 10.1111/bcpt.12261 -
International Journal of Molecular... Nov 2019Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during...
Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA's effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain.
Topics: Animals; Antineoplastic Agents, Phytogenic; Electroacupuncture; Gene Expression Regulation; Male; Myeloid Differentiation Factor 88; Neuralgia; Paclitaxel; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; TRPV Cation Channels; Toll-Like Receptor 4
PubMed: 31775332
DOI: 10.3390/ijms20235917