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Jiang J, Zhan L, Jiang B, Pan J, Hong C, Chen Z, Yang L. Anticancer therapy-induced peripheral neuropathy in solid tumors: diagnosis, mechanisms, and treatment strategies. Cancer Lett 2025; 620:217679. [PMID: 40154913 DOI: 10.1016/j.canlet.2025.217679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 03/21/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Anticancer therapy-induced peripheral neuropathy (PN) is a common adverse event during the diagnosis and treatment of solid tumors. The drug class, cumulative dose, and individual susceptibility affect the incidence and severity of PN. Owing to the lack of specific biomarkers and imaging tests, the diagnostic criteria for PN remain unclear. Moreover, the available and effective clinical treatment strategies are very limited, and most of the current drugs focus on symptom management rather than fundamental reversal of the disease course. The morbidity mechanisms of PN are diverse, including direct neurotoxicity, mitochondrial dysfunction, and disruption of axonal transport. Here, we summarize the diagnosis, mechanisms, and neuroprotective strategies of PN and discuss potential intervention treatments.
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Affiliation(s)
- Jiahong Jiang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Luying Zhan
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Boyang Jiang
- The Clinical Medical College, Hangzhou Normal University, Hangzhou, Zhejiang, China
| | - Jingyi Pan
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chaojin Hong
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zheling Chen
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
| | - Liu Yang
- Cancer Center, Department of Medical Oncology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Yang C, Song X, Sun H, Chen X, Liu C, Yang Y, Wang Z, Zhu J, Chen M. Peripheral Neuropathy in Patients With Ovarian Cancer Administrating Poly ADP-Ribose Polymerase Inhibitors: A Real-World Study Based on Bayesian Disproportionality Analysis of the US Food and Drug Administration Adverse Event Reporting System. Clin Ther 2025:S0149-2918(25)00160-2. [PMID: 40413120 DOI: 10.1016/j.clinthera.2025.04.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 04/05/2025] [Accepted: 04/25/2025] [Indexed: 05/27/2025]
Abstract
PURPOSE The aim of this study was to analyze adverse events in terms of safety signals and conduct pairwise comparisons on the constituent ratios of the reporting rates, severity, and outcomes of peripheral neuropathy among poly ADP-ribose polymerase inhibitors in the treatment of epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (collectively referred to as EOC) leveraging the US Food and Drug Administration Adverse Event Reporting System. METHODS Data on peripheral neuropathy reports related to EOC treatment submitted to the US Food and Drug Administration Adverse Event Reporting System from the first quarter of 2015 to the third quarter of 2024 were collected. Three poly ADP-ribose polymerase inhibitors are identified: olaparib, niraparib, and rucaparib. The primary composite end point of this study was the safety signals for peripheral neuropathy in patients with EOC receiving poly ADP-ribose polymerase inhibitors treatment, whereas the secondary end points included the safety signals for sensory neuropathy, autonomic neuropathy, and motor neuropathy. All analyses were conducted using Stata 18.0 MP software. FINDINGS A total of 300,810 eligible records were included, among which there were 70,332 reports of peripheral neuropathy. For the primary composite end point, a safety signal related to peripheral neuropathy was detected with niraparib (reporting odds ratio [ROR] = 1.47; information component [IC]025 = 0.21), whereas no safety signal was found with olaparib or rucaparib. For the secondary end points, safety signals related to autonomic, sensory, and motor neuropathies were detected with niraparib (ROR = 1.42, IC025 = 0.21; ROR = 1.39, IC025 = 0.20; ROR = 1.31, IC025 = 0.17), whereas no signals were identified with olaparib and rucaparib. IMPLICATIONS For patients with EOC, prudent surveillance of peripheral neuropathy is warranted when administrating niraparib. Certainly, more large-scale and long-term follow-up period studies were entailed.
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Affiliation(s)
- Chenguang Yang
- Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical College, Xuancheng, Anhui, China
| | - Xuan Song
- Department of General Medicine, Affiliated Xuancheng Hospital of Wannan Medical College, Xuancheng, Anhui, China
| | - Hongmei Sun
- Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical College, Xuancheng, Anhui, China
| | - Xi Chen
- Department of Epidemiology and Statistics, School of Public Health, Medical College, Zhejiang University, Hangzhou, Zhejiang, China
| | - Chengjiang Liu
- Department of General Medicine, Affiliated Anqing First People's Hospital of Anhui Medical University, Anqing, Anhui, China
| | - Yi Yang
- Department of Neurology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Zhongjian Wang
- BCPMdata Pharma Technology (Chengdu) Co., Ltd, Chengdu, Sichuan, China
| | - Jing Zhu
- Department of Reproductive Endocrinology, Center for Reproductive Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Min Chen
- Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical College, Xuancheng, Anhui, China.
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Xu J, Zhang Q, Xue N, Zhang C, Xu W. The therapeutic effect of acupuncture in the treatment of chemotherapy-induced peripheral neuropathy: a randomized controlled trial. Front Oncol 2025; 15:1500410. [PMID: 40308502 PMCID: PMC12040932 DOI: 10.3389/fonc.2025.1500410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 03/24/2025] [Indexed: 05/02/2025] Open
Abstract
Introduction Effective treatments for preventing and treating chemotherapy-induced peripheral neuropathy (CIPN) are still under exploration. Acupuncture in the treatment of CIPN requires more clinical trial data. This study aimed to evaluate the therapeutic effect of acupuncture on CIPN and explore its efficacy and safety in improving peripheral neuropathy. Methods A randomized controlled trial was conducted from May 2021 to June 2023. Eligible patients were randomly divided into a verum acupuncture group and a sham acupuncture group at a 1:1 ratio with sealed opaque envelopes. The patients of both the two groups took oral mecobalamin tablets, 0.5 mg, three times a day for 2 weeks. Participants received acupuncture treatment three times a week for 2 weeks. The primary outcome was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 3.0. The secondary outcomes were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-CIPN twenty-item subscale (QLQ-CIPN20), Numerical Rating Scale (NRS), Traditional Chinese Medicine (TCM) syndrome score, and nerve conduction study (NCS) testing. Assessments were conducted at baseline, 1 week, and 2 weeks. Results All 70 participants were recruited and randomized. In the end, 68 patients were included in the datasets and received verum acupuncture (n = 34) or sham acupuncture (n = 34). After 2 weeks of treatment and follow-up, a statistically significant difference was found in the NCI-CTCAE scores between the two groups (p = 0.02). Baseline-to-2-week assessment scores improved significantly in the intervention group (vs. controls) on EORTC QLQ-CIPN20 (p = 0.02), NRS scores (p = 0.03), TCM syndrome scores (p = 0.04), and sensory nerve action potential (SNAP) of median and peroneal nerves, sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of peroneal nerves (p < 0.05). No serious adverse events were reported. Conclusion This study supports the feasibility of acupuncture combined with medication as an intervention for patients with CIPN and confirms its efficacy and safety in improving peripheral neuropathy. Clinical Trial Registration The Chinese Clinical Trial Registry, identifier ChiCTR2100045762.
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Affiliation(s)
- Jinqun Xu
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
- Department of Oncology, Yibin Hospital of Traditional Chinese Medicine, Yibin, China
| | - Qing Zhang
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Na Xue
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Cui Zhang
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Weiru Xu
- Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
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Jones MK, Nicklawsky A, Shortt J, Pattee J, Kennerley V, Eule CJ, Candelario N, O'Donnell PH, Flaig TW. Pharmacogenomics of chemotherapy induced peripheral neuropathy using an electronic health record-derived definition: a genome-wide association study. Support Care Cancer 2025; 33:362. [PMID: 40198382 DOI: 10.1007/s00520-025-09392-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 03/22/2025] [Indexed: 04/10/2025]
Abstract
PURPOSE Prior studies evaluating the genetic predisposition to chemotherapy induced peripheral neuropathy (CIPN) have been limited by small populations due to difficulty with real-world data extraction. This genome-wide association study (GWAS) evaluates the genetic differences between patients who developed CIPN against those unaffected, using an electronic health record (EHR) definition of CIPN. METHODS This study included all patients who received chemotherapy associated with CIPN and had germline genetic data within the biobank at the Colorado Center for Personalized Medicine. CIPN was defined by a new neuropathic pain medication or an ICD-diagnosis of neuropathy after specified chemotherapy initiation. GWAS were stratified by (1) total population, (2) platinum chemotherapy, (3) taxane chemotherapy, and (4) vinca alkaloid chemotherapy. Genes previously associated with CIPN were analyzed within each GWAS. RESULTS Nine hundred fifteen patients received chemotherapy associated with CIPN, with 528 patients (57%) developing CIPN. Median age at chemotherapy initiation was 60.5 years; female sex (n = 517, 56.5%) and White or Caucasian race (n = 822, 89.8%) were most common. Among single nucleotide polymorphisms (SNPs) that reached suggestive levels of genome-wide significance (p < 1 × 10-5), 60 SNPs occurred within 11 genes that may play a role in the development of or protection against CIPN, including RCOR1, CLDN14, TRIM5, and TMC2. No SNPs previously associated with CIPN achieved genome-wide significance in this population. CONCLUSION This pharmacogenomic study suggests several genomic loci that may modulate the development of CIPN. This EHR-definition may allow for increased sample sizes and improved statistical power in future genetic studies of CIPN.
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Affiliation(s)
- Michael K Jones
- Internal Medicine Residency, University of Colorado School of Medicine, Aurora, CO, United States.
| | - Andrew Nicklawsky
- University of Colorado Cancer Center Biostatistics and Bioinformatics Shared Resource, Aurora, CO, United States
| | - Jonathan Shortt
- Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, United States
- The Biobank at the Colorado Center for Personalized Medicine, A Partnership Between UCHealth and the University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Jack Pattee
- Center for Innovative Design and Analysis, Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
- The Biobank at the Colorado Center for Personalized Medicine, A Partnership Between UCHealth and the University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Victoria Kennerley
- Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO, United States
- The Biobank at the Colorado Center for Personalized Medicine, A Partnership Between UCHealth and the University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Corbin J Eule
- Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, United States
| | - Nellowe Candelario
- Division of Hematology and Medical Oncology, Fred Hutchinson Cancer Center at University of Washington - Northwest Medical Campus, Seattle, WA, United States
| | - Peter H O'Donnell
- Department of Medicine and Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, United States
| | - Thomas W Flaig
- Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, United States
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Brownson-Smith R, Orange ST, Cresti N, Hunt K, Saxton J, Temesi J. Effect of exercise before and/or during taxane-containing chemotherapy treatment on chemotherapy-induced peripheral neuropathy symptoms in women with breast cancer: systematic review and meta-analysis. J Cancer Surviv 2025; 19:78-96. [PMID: 37615928 PMCID: PMC11813970 DOI: 10.1007/s11764-023-01450-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 08/13/2023] [Indexed: 08/25/2023]
Abstract
PURPOSE To systematically review and meta-analyse the efficacy of exercise interventions delivered before and/or during taxane-containing chemotherapy regimens on chemotherapy-induced peripheral neuropathy (CIPN), fatigue, and health-related quality of life (HR-QoL), in women with breast cancer. METHODS Seven electronic databases were systematically searched for randomised controlled trials (RCTs) reporting on the effects of exercise interventions in women with breast cancer receiving taxane-containing chemotherapeutic treatment. Meta-analyses evaluated the effects of exercise on CIPN symptoms, fatigue, and HR-QoL. RESULTS Ten trials involving exercise interventions ranging between 2 and 12 months were included. The combined results of four RCTs consisting of 171 participants showed a reduction in CIPN symptoms following exercise compared with usual care (standardised mean difference - 0.71, 95% CI - 1.24 to - 0.17, p = 0.012; moderate-quality evidence, I2 = 76.9%). Pooled results from six RCTs with 609 participants showed that exercise interventions before and/or during taxane-containing chemotherapy regimens improved HR-QoL (SMD 0.42, 95% CI 0.07 to 0.76, p = 0.03; moderate-quality evidence, I2 = 49.6%). There was no evidence of an effect of exercise on fatigue (- 0.39, 95% CI - 0.95 to 0.18, p = 0.15; very low-quality evidence, I2 = 90.1%). CONCLUSIONS This systematic review found reduced levels of CIPN symptoms and an improvement in HR-QoL in women with breast cancer who exercised before and/or during taxane-based chemotherapy versus usual care controls. IMPLICATIONS FOR CANCER SURVIVORS This evidence supports the role of exercise as an adjunctive treatment for attenuating the adverse effects of taxane-containing chemotherapy on CIPN symptoms and HR-QoL.
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Affiliation(s)
- Rosiered Brownson-Smith
- Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle Upon Tyne, UK.
| | - Samuel T Orange
- School of Biomedical, Nutritional and Sport Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle uponTyne, UK
- Newcastle University Centre for Cancer, Newcastle University, Newcastle-Upon-Tyne, UK
| | - Nicola Cresti
- Northern Centre for Cancer Care, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Katherine Hunt
- Northern Centre for Cancer Care, The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - John Saxton
- School of Sport, Exercise & Rehabilitation Sciences, University of Hull, Hull, UK
| | - John Temesi
- Department of Sport, Exercise and Rehabilitation, Faculty of Health and Life Sciences, Northumbria University, Newcastle Upon Tyne, UK
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Matsui Y, Kishi H, Matsui C, Morita J, Mizuno H, Mortada H, Sasaki H, Fukagai T. Novel Frostbite Cooling Device for Real-time Assessment and Prevention of Chemotherapy-induced Peripheral Neuropathy. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6423. [PMID: 39830441 PMCID: PMC11741218 DOI: 10.1097/gox.0000000000006423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Accepted: 11/07/2024] [Indexed: 01/22/2025]
Abstract
Background Chemotherapy-induced peripheral neuropathy (CIPN) affects 29%-68% of patients undergoing anticancer treatments within the first month. Traditional cryotherapy methods, such as frozen gloves, can pose risks. This study evaluates the cool-water electric circulation seat (CECS), which maintains a constant 15°C, as a safer alternative. Methods In this prospective study, 21 healthy Japanese adults underwent 2.5 hours of hand cooling at 15°C, reflecting the standard duration of taxane anticancer drug administration. Microcirculation was evaluated using videocapillaroscopy before and after cooling. Results Results showed significant reductions in blood vessel area and altered red blood cell movement postcooling. Finger temperature and vascular area decreased significantly (P < 0.001), and red blood cell movement changed significantly, with most cells shifting from slow (52.4%) or fast (47.6%) movement before cooling to slow (23.8%) or immobile (76.2%) afterward (P < 0.001). Thirty minutes postcooling, 38.1% of participants reported temporary redness, and 28.6% reported pain, both resolving by the next day. Conclusions The CECS effectively provides secure cooling, offering a promising approach for CIPN prevention without frostbite risk. These findings highlight the potential advantages of CECS in sustained cooling therapy for CIPN prevention.
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Affiliation(s)
- Yuki Matsui
- From the Department of Urology, Showa University School of Medicine; Tokyo, Japan
- Department of Urology, Hitachi Medical Center, Ibaraki, Japan
| | - Hirotaka Kishi
- From the Department of Urology, Showa University School of Medicine; Tokyo, Japan
- Department of Urology, Hitachi Medical Center, Ibaraki, Japan
| | - Chihiro Matsui
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Jun Morita
- From the Department of Urology, Showa University School of Medicine; Tokyo, Japan
- Department of Urology, Hitachi Medical Center, Ibaraki, Japan
| | - Hiroshi Mizuno
- Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hatan Mortada
- Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University and Department of Plastic Surgery and Burn Unit, King Saud Medical City, Riyadh, Saudi Arabia
| | - Haruaki Sasaki
- Department of Urology, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Takashi Fukagai
- From the Department of Urology, Showa University School of Medicine; Tokyo, Japan
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Casaril AM, Gaffney CM, Shepherd AJ. Animal models of neuropathic pain. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2024; 179:339-401. [PMID: 39580217 DOI: 10.1016/bs.irn.2024.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2024]
Abstract
Animal models continue to be crucial to developing our understanding of the molecular, cellular, and neurophysiological mechanisms that lead to neuropathic pain. The overwhelming majority of animal studies use rodent models, ranging from surgical and trauma-induced models to those induced by metabolic diseases, genetic mutations, viruses, neurotoxic drugs, and cancer. We discuss the clinical relevance of the available models and the pain behavior tests commonly used as outcome measures. Finally, we summarize the refinements that have been proposed to improve the ability of animal model studies to predict clinical efficacy.
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Affiliation(s)
- Angela M Casaril
- Laboratories of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Caitlyn M Gaffney
- Laboratories of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Andrew J Shepherd
- Laboratories of Neuroimmunology, Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
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Zenatri M, Perennec T, Michon C, Gernier F, Grellard JM, Piloquet FX, Dubot-Poitelon C, Kalbacher E, Tredan O, Augereau P, Pautier P, Fey L, Joly F, Frenel JS. Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study. Gynecol Oncol 2024; 187:139-144. [PMID: 38776631 DOI: 10.1016/j.ygyno.2024.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.
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Affiliation(s)
- M Zenatri
- Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France
| | - T Perennec
- Radiation Oncology Department, Institut de Cancerologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France
| | - C Michon
- Department of Biopathology, Institut de Cancerologie de l'Ouest, Centre Paul Papin, Angers, France
| | - F Gernier
- Clinical Research Department, Centre Francois Baclesse, Caen, France
| | - J-M Grellard
- Clinical Research Department, Centre Francois Baclesse, Caen, France
| | - F-X Piloquet
- Department of Medical Oncology, Institut de Cancerologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France
| | - C Dubot-Poitelon
- Medical Oncology Department, Centre Francois Baclesse, Unicaen University, Caen, France
| | - E Kalbacher
- Oncology Department, CHRU Besancon - Hopital Jean Minjoz, Besancon, France
| | - O Tredan
- Medical Oncology, Centre Léon Bérard, Lyon, France
| | - P Augereau
- Medical Oncology Department, Institut de Cancerologie de l'Ouest, Centre Paul Papin, Angers, France
| | - P Pautier
- Medicine Department, Institut Gustave Roussy, Villejuif, France
| | - L Fey
- Department of Biopathology, Institut de Cancerologie de l'Ouest, Centre Paul Papin, Angers, France
| | - F Joly
- Medical Oncology Department, Centre Francois Baclesse, Unicaen University, Caen, France
| | - J-S Frenel
- Medical Oncology Department, Institut de Cancerologie de l'Ouest, Centre Rene Gauducheau, GINECO Group and GINEGEPS, Saint-Herblain, France.
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9
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Cao Y, Jiang W, Yan F, Pan Y, Gei L, Lu S, Chen X, Huang Y, Yan Y, Feng Y, Li Q, Zeng W, Xing W, Chen D. Sex differences in PD-L1-induced analgesia in paclitaxel-induced peripheral neuropathy mice depend on TRPV1-based inhibition of CGRP. CNS Neurosci Ther 2024; 30:e14829. [PMID: 38961264 PMCID: PMC11222069 DOI: 10.1111/cns.14829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 06/13/2024] [Accepted: 06/16/2024] [Indexed: 07/05/2024] Open
Abstract
AIMS Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 μL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1β were measured via RT-PCR. RESULTS TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.
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Affiliation(s)
- Yan Cao
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Wenqi Jiang
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Fang Yan
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Yuyan Pan
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Liba Gei
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
- Department of AnesthesiologyPeking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University/Inner Mongolia Autonomous Region Cancer HospitalHohhotChina
| | - Simin Lu
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Xiangnan Chen
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
- Department of AnesthesiologyGuangdong Women and Children HospitalGuangzhouChina
| | - Yang Huang
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Yan Yan
- Department of AnesthesiologyHuizhou Municipal Central HospitalHuizhouChina
| | - Yan Feng
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Qiang Li
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Weian Zeng
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Wei Xing
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
| | - Dongtai Chen
- Department of Anesthesiology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for CancerSun Yat‐Sen University Cancer CenterGuangzhouChina
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Du C, Lu C, Li G, Deng D, Chen W. Electroacupuncture for oculomotor nerve palsy after chemotherapy: A case report. Medicine (Baltimore) 2024; 103:e38547. [PMID: 38875429 PMCID: PMC11175888 DOI: 10.1097/md.0000000000038547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 05/21/2024] [Indexed: 06/16/2024] Open
Abstract
INTRODUCTION Oculomotor nerve palsy (ONP) is often discovered in the ophthalmology department, manifested as ptosis with the same side, eyeball in the fixed external booth, or accompanied by limited inward, upward, and downward movements. The present case report described the effect of electroacupuncture (EA) on a breast cancer patient with ONP after chemotherapy. PATIENT CONCERNS A 56-year-old breast cancer patient presented with severe ptosis and fixed right eye exotropia. Besides, it is challenging to perform the movement inward, upward, and downward, and with obvious diplopia. DIAGNOSES The breast cancer patient was diagnosed with ONP, chemotherapy history. INTERVENTIONS The patient was introduced to acupuncture department to receiving EA treatment. OUTCOMES After 12 times of EA treatments, the symptom of ptosis was significantly improved, and the right upper eyelid can lift autonomously as same as the left eye. Besides, the patient's right lateral eye could move freely, and the symptoms of double vision disappeared. CONCLUSION The case suggests that EA may be an effective alternative treatment for ONP.
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Affiliation(s)
- Chun Du
- Tianshui and Wulin Street Community Health Service Center of Gongshu District, Hangzhou, China
| | - Chao Lu
- Department of Traditional Chinese Medicine, Zhejiang Cancer Hospital, Hangzhou, China
| | - Guangliang Li
- Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Dehou Deng
- Department of Traditional Chinese Medicine, Zhejiang Cancer Hospital, Hangzhou, China
| | - Weiji Chen
- Department of Acupuncture and Moxibustion, The Third Affiliated Hospital of Zhejiang Chinese Medical University (Zhongshan Hospital of Zhejiang Province), Hangzhou, China
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Anastasio MK, Unnithan S, Scott A, Hayes T, Shah S, Moss HA, Erkanli A, Havrilesky LJ. Cryocompression to Reduce Peripheral Neuropathy in Gynecologic Cancer: A Randomized Controlled Trial. Obstet Gynecol 2023; 142:1459-1467. [PMID: 37883997 DOI: 10.1097/aog.0000000000005419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 08/24/2023] [Indexed: 10/28/2023]
Abstract
OBJECTIVE To investigate the efficacy of cryocompression therapy to prevent chemotherapy-induced peripheral neuropathy. METHODS This single-institution, randomized, self-controlled trial of cryocompression enrolled gynecologic cancer patients planned for five to six cycles neurotoxic chemotherapy. Exclusion criteria were prior neurotoxic chemotherapy or baseline peripheral neuropathy. Participants were randomized to cryocompression on dominant versus non-dominant hand and foot (treatment), with no intervention on the opposite side (control). Compression socks and gloves and ice bags were applied 15 minutes before, during, and 15 minutes after infusion. Primary outcome measures included the PNQ (Patient Neurotoxicity Questionnaire) and the Semmes-Weinstein monofilament test; secondary outcomes included the FACT/GOG-NTX (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity) and patient acceptability and tolerability. Sixty patients completing the study were necessary to detect a 70% reduction in the odds of PNQ grade C or higher peripheral sensory neuropathy with 80% power. RESULTS Ninety-one patients were enrolled from January 2021 to October 2022; 69 were eligible for final analysis. Of the 91 patients, 64.8% were White, 30.8% were Black, and 1.1% were Hispanic or Latina. With successive cycles, more patients had sensory PNQ grade C or higher neuropathy on the control side compared with the cryocompression side. Cryocompression decreased the odds of sensory neuropathy (PNQ grade C or higher) by 46% at final visit (odds ratio 0.54, 95% CI 0.31-0.94; P =.03). There was no difference in tactile sensitivity based on the monofilament test between sides at the final visit. At the final visit, average FACT/GOG-NTX-11 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 11 Item Version) scores were significantly lower on the cryocompression than the control side (estimate -0.97, 95% CI -1.89 to -0.06; P =.04), as were FACT/GOG-NTX-4 (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version) scores (estimate -0.35, 95% CI -0.64 to -0.05; P =.02). More than 85% of patients assessed the intervention as acceptable and tolerable. CONCLUSIONS Cryocompression therapy reduces subjective chemotherapy-induced peripheral sensory neuropathy in patients who are receiving paclitaxel or cisplatin for gynecologic cancer. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT04563130.
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Affiliation(s)
- Mary Katherine Anastasio
- Department of Obstetrics and Gynecology, the Department of Biostatistics and Bioinformatics, the Department of Neurology, and the Duke Cancer Institute, Duke University Medical Center, and the Division of Gynecologic Oncology, Duke Cancer Institute, Durham, North Carolina
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12
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Kesireddy M, Tenner L. Colon Cancer Survivorship in Patients Who Have Received Adjuvant Chemotherapy. Clin Colorectal Cancer 2023; 22:361-374. [PMID: 37574392 DOI: 10.1016/j.clcc.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 07/07/2023] [Indexed: 08/15/2023]
Abstract
The number of colon cancer survivors in the United States is increasing due to improved early detection, better treatments that extend survival, and the growing aging population who are at high risk for cancer. Following initial active treatment, colon cancer survivors experience a wide range of long-term physical, psychological, and socio-economic effects that impact their overall well-being. Healthcare providers caring for survivors need to prioritize not only monitoring for cancer recurrence but also optimizing their overall health through addressing these long-term effects; managing their comorbidities; promoting healthy behaviors (like exercise, nutrition, and weight loss); and screening for a second primary cancer depending on their risk. Personalized survivorship care plans should be formulated clearly outlining the roles of various healthcare providers involved in their care. Our review article focuses on these various aspects of colon cancer survivorship, including surveillance for cancer recurrence specific to those who received adjuvant chemotherapy with curative intent.
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Affiliation(s)
- Meghana Kesireddy
- Division of Hematology-Oncology, University of Nebraska Medical Center- Fred & Pamela Buffett Cancer Center, Omaha, NE
| | - Laura Tenner
- Division of Hematology-Oncology, University of Nebraska Medical Center- Fred & Pamela Buffett Cancer Center, Omaha, NE.
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13
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Shi H, Yuan X, Fan W, Yang X, Liu G. An umbrella review of the evidence to guide decision-making in acupuncture therapies for chemotherapy-induced peripheral neuropathy. J Cancer Res Clin Oncol 2023; 149:15939-15955. [PMID: 37676268 DOI: 10.1007/s00432-023-05369-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/29/2023] [Indexed: 09/08/2023]
Abstract
BACKGROUND Acupuncture therapy is believed to have therapeutic potential for patients suffering from chemotherapy-induced peripheral neuropathy (CIPN). This umbrella review aims to summarize and evaluate the evidence from current systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of acupuncture treatment for CIPN. METHODS We conducted a comprehensive search in eight electronic databases for SRs/MAs that included RCTs on acupuncture treatment for CIPN. Two separate researchers independently evaluated the methodological quality, reporting quality, and evidence quality of the SRs/MAs that were included in the study. Additionally, we examined the extent of overlap among the included RCTs by calculating the corrected covered area (CCA). Furthermore, we assessed the dependability of the effect sizes by conducting excess significance tests. We conducted a quantitative synthesis of all RCTs included in the SRs/MAs to obtain objective and updated conclusions. Furthermore, we also conducted an analysis of the acupuncture points used in RCTs. RESULTS This umbrella review includes 9 SRs/MAs, and their methodological quality, risk of bias, reporting quality, and evidence quality were all deemed unsatisfactory. Out of the 9 SRs/MAs, 28 RCTs were included, with a total CCA of 25.4%, indicating a high degree of overlap. The test of super-significance did not yield any significant results. Our updated meta-analysis suggests that CIPN patients can benefit from acupuncture therapy, as indicated by effectiveness in measures including BPI-SF, VAS, FACT-NTX, NRS, SCV, and NCI-CTCAE. Egger's test and sensitivity analysis demonstrate the reliability and stability of this conclusion. The commonly used acupuncture points in the current RCTs include ST36, LI11, LI4, LR3, and SP6. CONCLUSION Based on the existing evidence, acupuncture is effective and safe for patients with CIPN, as it can significantly improve effective rate, pain symptoms, quality of life, and nerve conduction velocity. However, given the low quality of current evidence, we should be cautious in interpreting this conclusion.
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Affiliation(s)
- Hongshuo Shi
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xin Yuan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Weijing Fan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Xiao Yang
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Guobin Liu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Cheng F, Zhang R, Sun C, Ran Q, Zhang C, Shen C, Yao Z, Wang M, Song L, Peng C. Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies. Front Pharmacol 2023; 14:1231401. [PMID: 37593174 PMCID: PMC10427877 DOI: 10.3389/fphar.2023.1231401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/18/2023] [Indexed: 08/19/2023] Open
Abstract
Oxaliplatin-based chemotherapy is a standard treatment approach for colorectal cancer (CRC). However, oxaliplatin-induced peripheral neurotoxicity (OIPN) is a severe dose-limiting clinical problem that might lead to treatment interruption. This neuropathy may be reversible after treatment discontinuation. Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.
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Affiliation(s)
- Fang Cheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ruoqi Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chen Sun
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qian Ran
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Cuihan Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Changhong Shen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ziqing Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Miao Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lin Song
- Department of Pharmacy, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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15
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Guo S, Han W, Wang P, Wang X, Fang X. Effects of exercise on chemotherapy-induced peripheral neuropathy in cancer patients: a systematic review and meta-analysis. J Cancer Surviv 2023; 17:318-331. [PMID: 35149899 DOI: 10.1007/s11764-022-01182-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/03/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE Summarize and critically evaluate the existing studies to determine the effects of exercise on chemotherapy-induced peripheral neuropathy in cancer patients. METHODS We searched PubMed, Scopus, Web of Science, and Cochrane Library databases for randomized controlled trials reporting exercise intervention in cancer patients with chemotherapy-induced peripheral neuropathy. The outcomes of interest included chemotherapy-induced peripheral neuropathy symptoms, physical function (balance control, muscle strength, and functional status), and quality of life. The Cochrane Collaboration's tool was employed to assess the risk of bias. RESULTS The search identified 1309 studies, 16 of which eligible. Our meta-analysis revealed that exercise intervention significantly improved the quality of life (SMD = 0.83, 95% CI = 0.58 to 1.08, I2 = 0%, P < 0.00001) and relieved neuropathic pain (MD = - 4.93, 95% CI = - 5.60 to - 4.26, I2 = 0%, P < 0.00001). The muscular strength of the upper (SMD = 1.10, 95% CI = 0.68 to 1.51, I2 = 25%, P < 0.00001) and the lower limbs (SMD = 0.84, 95% CI = 0.42 to 1.26, I2 = 36%, P < 0.00001) increased and balance performance (SMD = 1.05, 95% CI = 0.62 to1.48, I2 = 0%, P < 0.00001) was better in the exercise group than in the group with usual care. However, no evidence was found that exercise intervention could improve CIPN symptoms. CONCLUSIONS The results of this study showed that combined exercise could be an effective option for improving quality of life, physical function (balance control and muscle strength), and neuropathic pain in cancer patients with chemotherapy-induced peripheral neuropathy. Further exploration of appropriate exercise prescriptions is needed to improve other outcomes. IMPLICATIONS FOR CANCER SURVIVORS Specific and appropriate exercise intervention for cancer patients with chemotherapy-induced peripheral neuropathy should be recommended because these interventions can improve their quality of life and physical function.
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Affiliation(s)
- Shaoning Guo
- School of Nursing, Jilin University, 965 Xinjiang Street, Changchun, 130021, Jilin, China
| | - Wenwen Han
- Department of Nursing, The First Bethune Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Pengju Wang
- Department of Nursing, The First Bethune Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Xue Wang
- School of Nursing, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Xuedong Fang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin, China.
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16
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Comparative Transcriptome of Dorsal Root Ganglia Reveals Distinct Etiologies of Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy in Rats. Neuroscience 2023; 516:1-14. [PMID: 36822350 DOI: 10.1016/j.neuroscience.2023.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/08/2023] [Accepted: 02/11/2023] [Indexed: 02/25/2023]
Abstract
Chemotherapy-induced peripheral neuropathy is one of the most common side effects of anticancer therapy. It is anticipated that chemotherapies with different mechanisms of action may affect somatosensory neurons differently. This study aimed to explore similar and differential etiologies of oxaliplatin- and paclitaxel-induced neuropathy by comparing the transcriptomes of dorsal root ganglia (DRGs). We retrieved our previously published transcriptome data of DRGs extracted from vehicle-, oxaliplatin- and paclitaxel-treated rats (GSE160543), to analyze in parallel the differentially expressed genes (DEGs) and Gene ontology (GO) terms enrichment. We found that both oxaliplatin and paclitaxel treatments consistently produced mechanical allodynia, thermal hyperalgesia, and cold hyperalgesia in rats. Compared to vehicle, 320 and 150 DEGs were identified after oxaliplatin and paclitaxel treatment, respectively. Only 17 DEGs were commonly dysregulated by the two reagents. Activating transcription factor 3 (Atf3), a marker of nerve injury, was elevated only after paclitaxel treatment. GO analysis suggested that paclitaxel treatment was associated with neuronal changes characterized by numerous terms that are related to synaptic transmission, while oxaliplatin was more likely to affect dividing cells (e.g., the glia) and neuroinflammation. Notably, 29 biological processes GO terms were commonly enriched in response to both drugs. However, 28 out of 29 terms were oppositely modulated. This study suggests that distinct mechanisms underly paclitaxel- and oxaliplatin-induced neuropathy. Paclitaxel might directly affect somatosensory neurons while oxaliplatin primarily targets dividing cells and immune cells.
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Zhi WI, Baser RE, Talukder D, Mei YZ, Harte SE, Bao T. Mechanistic and thermal characterization of acupuncture for chemotherapy-induced peripheral neuropathy as measured by quantitative sensory testing. Breast Cancer Res Treat 2023; 197:535-545. [PMID: 36527520 PMCID: PMC11218902 DOI: 10.1007/s10549-022-06846-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022]
Abstract
PURPOSE Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy. Acupuncture is a promising non-pharmacological intervention for CIPN. However, the physiological effects of acupuncture treatment remain poorly understood. We examined the effects of acupuncture on CIPN using semi-objective quantitative sensory testing (QST). METHODS We conducted a randomized controlled trial of real acupuncture (RA) and sham acupuncture (SA) compared to usual care (UC) in cancer survivors with moderate-to-severe CIPN. Treatment response was assessed with QST measures of tactile and vibration detection thresholds in hands and feet, thermal detection, and pain thresholds at weeks 0, 8, and 12. Constrained linear mixed model (cLMM) regression was used for statistical analysis. RESULTS 63 patients completed QST testing. At week 8, vibrational detection thresholds in feet were significantly lower in RA and SA (p = 0.019 and p = 0.046) than in UC, with no difference between RA and SA (p = 0.637). Both RA and SA also showed significantly higher cool thermal detection than UC (p = 0.008 and p = 0.013, respectively), with no difference between RA and SA (p = 0.790). No differences in tactile detection, vibrational detection in hands, warm thermal detection, and thermal pain thresholds were detected among the three arms at weeks 8 and 12. CONCLUSION QST demonstrated different patterns in RA, SA, and UC. After eight weeks of RA, we observed significant improvements in the vibrational detection threshold in feet and cool thermal detection threshold in hands compared to UC. No significant differences were seen when compared to SA. TRIAL REGISTRATION ClinicalTrials.gov (NCT03183037); June 9, 2017.
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Affiliation(s)
- W Iris Zhi
- Breast Medicine Service, Department of Medicine, Solid Tumor Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Raymond E Baser
- Department of Epidemiology and Biostatistics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Dristi Talukder
- Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ying Zi Mei
- Barnard College, Columbia University, New York, NY, USA
| | - Steven E Harte
- Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Ting Bao
- Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 321 East 61st Street, Room 458, New York, NY, 10065, USA.
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Mysona D, Dorr K, Ward A, Shaver E, Rungruang B, Ghamande S. Pharmacogenetics as a predictor chemotherapy induced peripheral neuropathy in gynecologic cancer patients treated with Taxane-based chemotherapy. Gynecol Oncol 2023; 168:114-118. [PMID: 36434945 DOI: 10.1016/j.ygyno.2022.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/20/2022] [Accepted: 10/25/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy. METHODS Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables. RESULTS Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001). CONCLUSIONS Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.
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Affiliation(s)
- David Mysona
- The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA; Center for Biotechnology and Genomic Medicine at Augusta University, Augusta, GA 30912, USA
| | - Katherine Dorr
- The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA
| | - Alex Ward
- The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA
| | - Ellen Shaver
- Consultative Genomix, Peachtree Corners, GA 30092, USA
| | - Bunja Rungruang
- The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA; Augusta University Medical Center, Department of Obstetrics & Gynecology, Augusta, GA 30912, USA
| | - Sharad Ghamande
- The Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA; Augusta University Medical Center, Department of Obstetrics & Gynecology, Augusta, GA 30912, USA.
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Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons. Biomolecules 2022; 12:biom12121873. [PMID: 36551301 PMCID: PMC9775584 DOI: 10.3390/biom12121873] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/06/2022] [Accepted: 12/10/2022] [Indexed: 12/15/2022] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve endings. Novel therapeutic agents might help to mitigate or prevent Paclitaxel toxicity on dorsal root ganglion (DRG) neurons. Thus, we used primary DRG neurons as a model to investigate the potential neuroprotective effects of the endocannabinoid-like substance, palmitoylethanolamide (PEA). DRG neurons were isolated from cervical to sacral segments of spinal nerves of Wister rats (6-8 weeks old). After isolation and purification of neuronal cell populations, different concentrations of Paclitaxel (0.01-10 µM) or PEA (0.1-10 µM) or their combination were tested on cell viability by MTT assay at 24 h, 48, and 72 h post-treatment. Furthermore, morphometric analyses of neurite length and soma size for DRG neurons were performed. Adverse Paclitaxel effects on cell viability were apparent at 72 h post-treatment whereas Paclitaxel significantly reduced the neurite length in a concentration-dependent manner nearly at all investigated time points. However, Paclitaxel significantly increased the size of neuronal cell bodies at all time windows. These phenotypic effects were significantly reduced in neurons additionally treated with PEA, indicating the neuroprotective effect of PEA. PEA alone led to a significant increase in neuron viability regardless of PEA concentrations, apparent improvements in neurite outgrowth as well as a significant decrease in soma size of neurons at different investigated time points. Taken together, PEA showed promising protective effects against Paclitaxel-related toxicity on DRG neurons.
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Wu X, Dai Y, Nie K. Research Progress of Liujunzi Decoction in the Treatment of Tumor-Associated Anorexia. Drug Des Devel Ther 2022; 16:1731-1741. [PMID: 35698654 PMCID: PMC9188393 DOI: 10.2147/dddt.s365292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/26/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Xipei Wu
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Yongzhao Dai
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
| | - Ke Nie
- School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China
- Correspondence: Ke Nie, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China, Email ;
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de Clauser L, Kappert C, Sondermann JR, Gomez-Varela D, Flatters SJL, Schmidt M. Proteome and Network Analysis Provides Novel Insights Into Developing and Established Chemotherapy-Induced Peripheral Neuropathy. Front Pharmacol 2022; 13:818690. [PMID: 35250568 PMCID: PMC8895144 DOI: 10.3389/fphar.2022.818690] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/12/2022] [Indexed: 01/09/2023] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side-effect of cancer therapies. So far, the development of CIPN cannot be prevented, neither can established CIPN be reverted, often leading to the cessation of necessary chemotherapy. Thus, there is an urgent need to explore the mechanistic basis of CIPN to facilitate its treatment. Here we used an integrated approach of quantitative proteome profiling and network analysis in a clinically relevant rat model of paclitaxel-induced peripheral neuropathy. We analysed lumbar rat DRG at two critical time points: (1) day 7, right after cessation of paclitaxel treatment, but prior to neuropathy development (pre-CIPN); (2) 4 weeks after paclitaxel initiation, when neuropathy has developed (peak-CIPN). In this way we identified a differential protein signature, which shows how changes in the proteome correlate with the development and maintenance of CIPN, respectively. Extensive biological pathway and network analysis reveals that, at pre-CIPN, regulated proteins are prominently implicated in mitochondrial (dys)function, immune signalling, neuronal damage/regeneration, and neuronal transcription. Orthogonal validation in an independent rat cohort confirmed the increase of β-catenin (CTNNB1) at pre-CIPN. More importantly, detailed analysis of protein networks associated with β-catenin highlights translationally relevant and potentially druggable targets. Overall, this study demonstrates the enormous value of combining animal behaviour with proteome and network analysis to provide unprecedented insights into the molecular basis of CIPN. In line with emerging approaches of network medicine our results highlight new avenues for developing improved therapeutic options aimed at preventing and treating CIPN.
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Affiliation(s)
- Larissa de Clauser
- Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy
- *Correspondence: Larissa de Clauser, ; Manuela Schmidt,
| | - Christin Kappert
- Max Planck Institute of Experimental Medicine, Goettingen, Germany
| | - Julia R. Sondermann
- Division of Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria
| | - David Gomez-Varela
- Division of Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria
| | - Sarah J. L. Flatters
- Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
| | - Manuela Schmidt
- Division of Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Vienna, Vienna, Austria
- *Correspondence: Larissa de Clauser, ; Manuela Schmidt,
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22
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Liu YW, Chen YJ, Chen YH, Tsai MY. Therapeutic Efficacy of Traditional Chinese Medicine Syndrome-Based Formulae to Neuropathic Pain Caused by Chemotherapy. Integr Cancer Ther 2022; 21:15347354221121095. [PMID: 36154520 PMCID: PMC9515521 DOI: 10.1177/15347354221121095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective: Chemotherapy-induced neuropathic pain (CINP) is a troublesome complication of
anti-cancer treatment. The aim of this retrospective study was to
investigate the effectiveness of classic Chinese herbal formulae (CHF) Huang
Qi Gui Zhi Wu Wu Tang (HQGZWWT) and Dang Gui Si Ni Tang (DGSNT) in the
treatment of CINP. Materials and Methods: Douleur Neuropathique 4 (DN4) and Functional Assessment of Cancer
Therapy-General (FACT-G) questionnaires were rated at baseline and after
3-monthly CHF treatment. Results: By searching through our medical records of all the CIPN patients from 2018
to 2019, we identified and enrolled 37 patients with Deficiency-Cold
syndrome in the study, for whom the treatment of neuropathic pain by regular
pharmacotherapies had failed or intolerable. At the third month evaluation
with the DN4 questionnaire, 13 patients had symptomatic remission, 15
patients remained stable, and 9 patients had no response to CHF. The 3-month
mean DN4 score was significantly higher than that at the baseline
(P < .001). After CHF treatment, significant
differences in quality of life were noted in the physical, social,
emotional, and functional well-being subscales, and in the total score, of
the FACT-G (P < .001). No adverse events or instances of
disease progression were observed. Conclusions: The results of our small study are the first in the literature to show the
clinical effectiveness of CHF for CINP. Combination of HQGZWWT and DGSNT is
well tolerated and may offer the possibility to ameliorate CINP more than
conventional care can. It merits further investigation.
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Affiliation(s)
- Yan-Wen Liu
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ying-Jung Chen
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yen-Hao Chen
- Division of Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Yen Tsai
- Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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23
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Tsai CH, Lin YH, Li YS, Ho TL, Hoai Thuong LH, Liu YH. Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci 2021; 22:ijms22179257. [PMID: 34502166 PMCID: PMC8430591 DOI: 10.3390/ijms22179257] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/20/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.
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Affiliation(s)
- Chih-Hung Tsai
- Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan; (C.-H.T.); (Y.-H.L.); (Y.-S.L.)
- Department of Neurology, National Taiwan University Hospital Yunlin Branch, Yunlin 64041, Taiwan
| | - Yuan-Ho Lin
- Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan; (C.-H.T.); (Y.-H.L.); (Y.-S.L.)
- Department of Chinese Medicine of E-Da Cancer Hospital, Kaohsiung 82445, Taiwan
| | - Yung-Sheng Li
- Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan; (C.-H.T.); (Y.-H.L.); (Y.-S.L.)
- Department of Chinese Medicine of Jiannren Hospital, Kaohsiung 811504, Taiwan
| | - Trung-Loc Ho
- International Master’s Program of Biomedical Sciences, China Medical University, Taichun 40402, Taiwan; (T.-L.H.); (L.H.H.T.)
| | - Le Huynh Hoai Thuong
- International Master’s Program of Biomedical Sciences, China Medical University, Taichun 40402, Taiwan; (T.-L.H.); (L.H.H.T.)
| | - Yu-Huei Liu
- Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan; (C.-H.T.); (Y.-H.L.); (Y.-S.L.)
- Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 40402, Taiwan
- Drug Development Center, China Medical University, Taichung 40402, Taiwan
- Correspondence: ; Tel.: +886-4-22052121 (ext. 2044)
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24
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Oneda E, Meriggi F, Zanotti L, Zaina E, Bighè S, Andreis F, Rueda S, Zaniboni A. Innovative Approach for the Prevention of Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Pilot Study With the Hilotherm Device, the Poliambulanza Hospital Experience. Integr Cancer Ther 2021; 19:1534735420943287. [PMID: 32856475 PMCID: PMC7457652 DOI: 10.1177/1534735420943287] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of taxanes, with no effective prevention or treatment available and a highly negative impact on patient quality of life. The aim of this study is to asses that the constant application of cooled cuffs on the hands and feet prevent and mitigate CIPN. METHODS Patients with breast, gynecologic, and pancreatic cancer who received weekly paclitaxel (PTX), PTX/carboplatin, and nab-paclitaxel (nab-PTX)/gemcitabine for any indication at the therapeutic scheduled dosage were included in this prospective study. Hilotherm Chemo care device forms a closed-loop system with cuffs and tubes through which a coolant flows at a temperature of 10 °C. CIPN was monitored using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (edition 3.0), and the tolerability and side effects were scored by using the Common Terminology Criteria for Adverse Events (T4.03 2017). RESULTS To date, we have enrolled 64 patients. Of these, 54 (84%) completed all cooling cycles. Continuous cooling was well tolerated by all patients. No patients had grade >2 CIPN or had serious or lasting adverse events as a result of Hilotherapy. The median time to CIPN onset was 77 days for the entire population. CONCLUSION Hilotherapy has good effectiveness and tolerability and seems to be able to prevent or reduce the symptoms of CIPN. We are still recruiting patients to obtain more data and to collect data at 3 months after the end of chemotherapy. Prospective studies seem to be warranted.
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Affiliation(s)
| | | | | | | | - Sara Bighè
- Fondazione Poliambulanza, Brescia, Italy
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25
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Amiri A, Chovanec M, Oliva V, Sedliak M, Mego M, Ukropec J, Ukropcová B. Chemotherapy-induced toxicity in patients with testicular germ cell tumors: The impact of physical fitness and regular exercise. Andrology 2021; 9:1879-1892. [PMID: 34245663 DOI: 10.1111/andr.13078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/04/2021] [Accepted: 07/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Testicular germ cell tumors (TGCTs) represent ∼95% of testicular malignancies and are the most common type of malignancy in young male adults. While the incidence of TGCTs has increased during the last decades, the advances in treatment, namely introducing cisplatin into the chemotherapy regimen, have made TGCTs highly curable with the 10-year survival rate exceeding 95%. However, in parallel with increased cure rates, survivors may experience acute and late adverse effects of treatment, which increase morbidity, reduce the quality of life, and can be potentially life-threatening. Chemotherapy-related toxicities include cardiovascular and metabolic diseases, secondary cancer, avascular necrosis, cognitive impairment, cancer-related fatigue, poor mental health-related quality of life, nephrotoxicity, hypogonadism, neurotoxicity, pulmonary toxicity, anxiety, and depression. These treatment-related adverse effects have emerged as important survivorship dilemmas in TGCT cancer survivors. Recently, regular physical exercise has increasingly attracted research and clinical attention as an adjunct therapy for cancer patients. PURPOSE Herein, we review the most common chemotherapy-related adverse effects in TGCT survivors and clinical relevance of exercise and increased cardio-respiratory fitness in modulating chemotherapy-related toxicity and quality of life in this population. RESULTS AND CONCLUSION Exercise has positive effects on a spectrum of physical and psychosocial outcomes during and after cancer treatment, and current guidelines on exercise prescription in chronic diseases define the recommended dose (volume and intensity) of regular exercise for cancer survivors, highlighting regular, sufficiently intensive physical activity as an essential part of patients' care.
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Affiliation(s)
- Ali Amiri
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Michal Chovanec
- 2nd, Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Viktor Oliva
- Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia
| | - Milan Sedliak
- Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia
| | - Michal Mego
- 2nd, Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia
| | - Jozef Ukropec
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Barbara Ukropcová
- Department of Metabolic Disease Research & Center of Physical Activity Research, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.,Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
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26
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Selvido DI, Bhattarai BP, Rokaya D, Niyomtham N, Wongsirichat N. Pain in Oral and Maxillofacial Surgery and Implant Dentistry: Types and Management. Eur J Dent 2021; 15:588-598. [PMID: 34041732 PMCID: PMC8382502 DOI: 10.1055/s-0041-1725212] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Over the years, the pain has been defined numerous times in several ways. In oral and maxillofacial surgery, the occurrence of pain, especially postoperatively, is anticipated. Pain arises as a combination of various processes after tissue damage. Distinct pain experiences in oral surgery were depicted in several previous studies, adding knowledge to the field. The management of these encounters has been suggested over time, improving treatment approaches in the clinical setting. This review aims to understand the pain and its types and intervention in the field of oral and maxillofacial surgery.
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Affiliation(s)
- Diane Isabel Selvido
- Department of Clinical Dentistry, Walailak University International College of Dentistry, Walailak University, Bangkok, Thailand
| | - Bishwa Prakash Bhattarai
- Department of Clinical Dentistry, Walailak University International College of Dentistry, Walailak University, Bangkok, Thailand
| | - Dinesh Rokaya
- Department of Clinical Dentistry, Walailak University International College of Dentistry, Walailak University, Bangkok, Thailand
| | - Nattisa Niyomtham
- Department of Clinical Dentistry, Walailak University International College of Dentistry, Walailak University, Bangkok, Thailand
| | - Natthamet Wongsirichat
- Department of Clinical Dentistry, Walailak University International College of Dentistry, Walailak University, Bangkok, Thailand
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27
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Oneda E, Abeni C, Zanotti L, Zaina E, Bighè S, Zaniboni A. Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention. World J Clin Oncol 2021; 12:458-467. [PMID: 34189069 PMCID: PMC8223716 DOI: 10.5306/wjco.v12.i6.458] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/29/2021] [Accepted: 06/04/2021] [Indexed: 02/06/2023] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.
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Affiliation(s)
- Ester Oneda
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Chiara Abeni
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Laura Zanotti
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Elisabetta Zaina
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Sara Bighè
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
| | - Alberto Zaniboni
- Department of Clinical Oncology, Fondazione Poliambulanza, Brescia 25124, Italy
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28
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surveillance and Survivorship Care of Patients After Curative Treatment of Colon and Rectal Cancer. Dis Colon Rectum 2021; 64:517-533. [PMID: 33591043 DOI: 10.1097/dcr.0000000000001984] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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29
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Sarezky J, Sachs G, Elinzano H, Stavros K. Cancer and Peripheral Nerve Disease. Clin Geriatr Med 2021; 37:289-300. [PMID: 33858611 DOI: 10.1016/j.cger.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Patients with cancer may experience neuropathy at any stage of malignancy, ranging from symptoms that are the earliest signs of cancer to side effects of treatment. Peripheral nerves are affected most commonly in a symmetric, stocking-glove pattern. Sensory neuronopathies, plexopathies, and radiculopathies may also be seen. The most common type of neuropathy in patients with cancer is related to chemotherapy, and recently peripheral nerve complications have been described as an effect of immune checkpoint inhibitors too. Other causes include paraneoplastic syndromes, direct tumor infiltration, and radiation. Treatment focuses on addressing the underlying cancer and management of neuropathic pain.
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Affiliation(s)
- Jonathan Sarezky
- Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street APC5, Providence, RI 02903, USA
| | - George Sachs
- Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street APC5, Providence, RI 02903, USA
| | - Heinrich Elinzano
- Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street APC5, Providence, RI 02903, USA
| | - Kara Stavros
- Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street APC5, Providence, RI 02903, USA.
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30
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Calls A, Torres-Espin A, Navarro X, Yuste VJ, Udina E, Bruna J. Cisplatin-induced peripheral neuropathy is associated with neuronal senescence-like response. Neuro Oncol 2021; 23:88-99. [PMID: 32597980 PMCID: PMC7850121 DOI: 10.1093/neuonc/noaa151] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Cisplatin-induced peripheral neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology of CIPN is poorly understood, so the chance of developing neuroprotective treatment is reduced. The aim of this study was to determine the exact mechanisms involved in CIPN development. METHODS By single-cell RNA-sequencing (scRNAseq), we have studied the transcriptomic profile of DRG sensory neurons from a well-characterized neurophysiological mouse model of CIPN. RESULTS Gene Ontology analysis of the scRNAseq data indicated that cisplatin treatment induces the upregulation of biological pathways related to DNA damage response (DDR) in the DRG neuronal population. Moreover, DRG neurons also upregulated the Cdkn1a gene, confirmed later by the measurement of its protein product p21. While apoptosis activation pathways were not observed in DRG sensory neurons of cisplatin-treated mice, these neurons did express several senescence hallmarks, including senescence-associated β-galactosidase, phospho-H2AX, and nuclear factor kappa B (Nfkb)-p65 proteins. CONCLUSIONS In this study, we determined that after cisplatin-induced DNA damage, p21 appears as the most relevant downstream factor of the DDR in DRG sensory neurons in vivo, which survive in a nonfunctional senescence-like state.
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Affiliation(s)
- Aina Calls
- Department of Cell Biology, Physiology, and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, Spain
- Biomedical Research Center Network on Neurodegenerative Diseases (CIBERNED), Bellaterra, Spain
| | - Abel Torres-Espin
- Department of Neurological Surgery, Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA
| | - Xavier Navarro
- Department of Cell Biology, Physiology, and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, Spain
- Biomedical Research Center Network on Neurodegenerative Diseases (CIBERNED), Bellaterra, Spain
| | - Victor J Yuste
- Department of Biochemistry, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, Spain
| | - Esther Udina
- Department of Cell Biology, Physiology, and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, Spain
- Biomedical Research Center Network on Neurodegenerative Diseases (CIBERNED), Bellaterra, Spain
| | - Jordi Bruna
- Department of Cell Biology, Physiology, and Immunology, Institute of Neuroscience, Autonomous University of Barcelona, Bellaterra, Spain
- Biomedical Research Center Network on Neurodegenerative Diseases (CIBERNED), Bellaterra, Spain
- Unit of Neuro-Oncology, Bellvitge Institute for Biomedical Research, L'Hospitalet de Llobregat, Barcelona, Spain
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31
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Recalde M, Miguel C, Noya-Riobó M, González S, Villar M, Coronel M. Resveratrol exerts anti-oxidant and anti-inflammatory actions and prevents oxaliplatin-induced mechanical and thermal allodynia. Brain Res 2020; 1748:147079. [DOI: 10.1016/j.brainres.2020.147079] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 07/27/2020] [Accepted: 08/21/2020] [Indexed: 12/30/2022]
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32
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Sphar BG, Bowe C, Dains JE. The Impact of Peripheral Cooling on Chemotherapy-Induced Peripheral Neuropathy: An Integrative Review. J Adv Pract Oncol 2020; 11:845-857. [PMID: 33489425 PMCID: PMC7810270 DOI: 10.6004/jadpro.2020.11.8.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent, potentially long-lasting side effect of select chemotherapies. It contributes to suboptimal chemotherapy dosing, and its symptoms negatively impact patients’ quality of life. To date, interventions to effectively prevent this toxicity have not been established, and interventions to treat CIPN have produced only modest results. The purpose of this integrative review is to examine the impact of regional cooling applied to distal extremities on the severity of CIPN. A literature review was performed using SCOPUS and PubMed databases. The search was not restricted by date but was restricted to English language. Forty-two articles were identified in the search, and six were included in the review after applying inclusion and exclusion criteria. Results related to protective effects from peripheral cooling against CIPN were variable. Four out of six studies demonstrated benefit of peripheral cooling in reducing the severity of CIPN. There was evidence to suggest that applying a relatively greater degree of cooling compared with a lesser degree may confer benefit in reducing the severity of CIPN. Both direct application of cooling and use of compression to achieve fingertip cooling showed potential benefit.
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Affiliation(s)
- Bethany G Sphar
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Christi Bowe
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Joyce E Dains
- The University of Texas MD Anderson Cancer Center, Houston, Texas
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33
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Li D, Yoo JH, Kim SK. Long-Lasting and Additive Analgesic Effects of Combined Treatment of Bee Venom Acupuncture and Venlafaxine on Paclitaxel-Induced Allodynia in Mice. Toxins (Basel) 2020; 12:toxins12100620. [PMID: 32998357 PMCID: PMC7600305 DOI: 10.3390/toxins12100620] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 09/18/2020] [Accepted: 09/25/2020] [Indexed: 12/11/2022] Open
Abstract
Paclitaxel, a primary chemotherapeutic agent used to treat numerous solid malignancies, is commonly associated with debilitating peripheral neuropathy. However, a satisfactory gold-standard monotherapy for this neuropathic pain is not currently available. A combination strategy of two or more medications with different properties may achieve more beneficial effects than monotherapy. Thus, we investigated the analgesic efficacies and spinal mechanisms of the combination strategy, including bee venom acupuncture (BVA) and venlafaxine (VLX) against paclitaxel-induced allodynia in mice. Four intraperitoneal infusions of paclitaxel on alternating days (2 mg/kg/day) induced cold and mechanical allodynia for at least 1 week as assessed using acetone and the von Frey hair test, respectively. Co-treatment of BVA (1.0 mg/kg, s.c., ST36) with VLX (40 mg/kg, i.p.) at the medium dose produced a longer-lasting and additive effect than each monotherapy at the highest dose (BVA, 2.5 mg/kg; VLX, 60 mg/kg). Spinal pre-administration of idazoxan (α2-adrenergic receptor antagonist, 10 μg), methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 10 μg), or MDL-72222 (5-HT3 receptor antagonist, 10 μg) abolished this analgesia. These results suggest that the combination therapy with BVA and VLX produces long-lasting and additive analgesic effects on paclitaxel-induced allodynia, via the spinal noradrenergic and serotonergic mechanism, providing a promising clinical strategy.
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Affiliation(s)
- Daxian Li
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea;
| | - Ju Hyuk Yoo
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea;
| | - Sun Kwang Kim
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea;
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea;
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea
- Correspondence:
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34
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Neurotoxicity of antineoplastic drugs: Mechanisms, susceptibility, and neuroprotective strategies. Adv Med Sci 2020; 65:265-285. [PMID: 32361484 DOI: 10.1016/j.advms.2020.04.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 02/06/2023]
Abstract
This review summarizes the adverse effects on the central and/or peripheral nervous systems that may occur in response to antineoplastic drugs. In particular, we describe the neurotoxic side effects of the most commonly used drugs, such as platinum compounds, doxorubicin, ifosfamide, 5-fluorouracil, vinca alkaloids, taxanes, methotrexate, bortezomib and thalidomide. Neurotoxicity may result from direct action of compounds on the nervous system or from metabolic alterations produced indirectly by these drugs, and either the central nervous system or the peripheral nervous system, or both, may be affected. The incidence and severity of neurotoxicity are principally related to the dose, to the duration of treatment, and to the dose intensity, though other factors, such as age, concurrent pathologies, and genetic predisposition may enhance the occurrence of side effects. To avoid or reduce the onset and severity of these neurotoxic effects, the use of neuroprotective compounds and/or strategies may be helpful, thereby enhancing the therapeutic effectiveness of antineoplastic drug.
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35
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The use of intraoperative radiation therapy in the management of locally recurrent rectal cancer. SEMINARS IN COLON AND RECTAL SURGERY 2020. [DOI: 10.1016/j.scrs.2020.100763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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36
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Battisti NML, Liposits G, De Glas NA, Gomes F, Baldini C, Mohile S. Systemic Therapy of Common Tumours in Older Patients: Challenges and Opportunities. A Young International Society of Geriatric Oncology Review Paper. Curr Oncol Rep 2020; 22:98. [PMID: 32725503 DOI: 10.1007/s11912-020-00958-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW Decision-making for systemic treatments in older patients with cancer is difficult because of concerns for decreased organ function, risk of toxicity, limited life expectancy due to comorbidities and the lack of evidence available to guide its management in this population. Here, we review the data on the role of systemic agents for the treatment of common malignancies in this age group. RECENT FINDINGS Evidence on the use of systemic treatments for older patients with cancer is increasing, especially for newer options including immune checkpoint inhibitors and targeted agents that provide comparable benefit in older and younger patients. Nonetheless, the risks for short- and long-term toxicities need to be considered. More research is warranted and represents a unique opportunity to increase the knowledge on cancer treatment for older adults. Healthy, older individuals should be considered for standard systemic treatment options, whereas those at risk based on geriatric assessments require adjusted plans. Geriatric assessments are key for decision-making.
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Affiliation(s)
- Nicolò Matteo Luca Battisti
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, UK. .,Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
| | - Gabor Liposits
- Department of Oncology, Regional Hospital West Jutland, Gl Landevej 61, 7400, Herning, Denmark
| | - Nienke Aafke De Glas
- Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333, Leiden, ZA, Netherlands
| | - Fabio Gomes
- Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Capucine Baldini
- Drug Development Department, Institut Gustave Roussy, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800, Villejuif, France
| | - Supriya Mohile
- Division of Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Ave # 704, Rochester, NY, 14642, USA
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Micheli L, Di Cesare Mannelli L, Del Bello F, Giannella M, Piergentili A, Quaglia W, Carrino D, Pacini A, Ghelardini C. The Use of the Selective Imidazoline I 1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity. Neurotherapeutics 2020; 17:1005-1015. [PMID: 32572830 PMCID: PMC7609613 DOI: 10.1007/s13311-020-00873-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Anti-cancer therapy based on the repeated administration of oxaliplatin is limited by the development of a disabling neuropathic syndrome with detrimental effects on the patient's quality of life. The lack of effective pharmacological approaches calls for the identification of innovative therapeutic strategies based on new targets. We focused our attention on the imidazoline I1 receptor (I1-R) and in particular on the selective I1-R agonist 2-(1-([1,1'-biphenyl]-2-yl)propan-2-yl)-4,5-dihydro-1H-imidazole) (carbophenyline). The purpose of this work was the preclinical evaluation of the efficacy of carbophenyline on oxaliplatin-induced neuropathic pain in mice. Carbophenyline, acutely per os administered (0.1-10 mg kg-1), induced a dose-dependent anti-hyperalgesic effect that was completely blocked by the pre-treatment with the I1-R antagonist 3 or the I1/α2 receptor antagonist efaroxan, confirming the I1-R-dependent mechanism. Conversely, pre-treatment with the I2-R antagonist BU224 did not block the anti-nociceptive effect evoked by carbophenyline. Repeated oral administrations of carbophenyline (1 mg kg-1) for 14 days, starting from the first day of oxaliplatin injection, counteracted the development of neuropathic pain in all behavioral tests (cold plate, Von Frey, and paw pressure tests) carried out 24 h after the last carbophenyline treatment on days 7 and 14. In the dorsal horn of the spinal cord, carbophenyline significantly decreased the oxaliplatin-induced astrocyte activation detected by immunofluorescence staining by the specific labelling with GFAP antibody. In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect against oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I1-R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain.
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Affiliation(s)
- Laura Micheli
- Dept. of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
| | - Lorenzo Di Cesare Mannelli
- Dept. of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy.
| | - Fabio Del Bello
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, 62032, Camerino, Italy
| | - Mario Giannella
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, 62032, Camerino, Italy
| | - Alessandro Piergentili
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, 62032, Camerino, Italy
| | - Wilma Quaglia
- School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Via S. Agostino 1, 62032, Camerino, Italy
| | - Donatello Carrino
- Department of Experimental and Clinical Medicine, Anatomy and Histology Section, University of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Alessandra Pacini
- Department of Experimental and Clinical Medicine, Anatomy and Histology Section, University of Florence, Largo Brambilla 3, 50134, Florence, Italy
| | - Carla Ghelardini
- Dept. of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Gaetano Pieraccini 6, 50139, Florence, Italy
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Oxaliplatin-induced peripheral neuropathy: clinical features, mechanisms, prevention and treatment. J Neurol 2020; 268:3269-3282. [PMID: 32474658 DOI: 10.1007/s00415-020-09942-w] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/18/2020] [Accepted: 05/20/2020] [Indexed: 02/06/2023]
Abstract
Oxaliplatin (OXA) is a commonly used platinum-based chemotherapy drug for colorectal cancer. OXA-induced peripheral neurotoxcity (OIPN) is a comprehensive adverse reaction of OXA. OIPN can be divided into acute and chronic types according to clinical features and different mechanisms. The main clinical features of acute OIPN are cold-sensitive sensory symptoms and neuropathic pain in limbs. In addition to the above symptoms, chronic OIPN also produces autonomic nerve dysfunction. The most important mechanism involved in acute OIPN is the alteration of voltage-gated Na + channels, and nuclear DNA damage in chronic OIPN. There are some methods like reducing exposure to cold, calcium and magnesium salts, amifostine could be beneficial in acute OIPN prevention and dose modification, changing in schedule glutathione, duloxetine, selective serotonin reuptake inhibitors, carbonic anhydrase inhibitor in chronic OIPN prevention. Recent updates are provided in this article in relation to the clinical features, potential mechanisms, prevention and treatment of OIPN.
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Bennedsgaard K, Ventzel L, Themistocleous AC, Bennett DL, Jensen AB, Jensen AR, Andersen NT, Jensen TS, Tankisi H, Finnerup NB. Long-term symptoms of polyneuropathy in breast and colorectal cancer patients treated with and without adjuvant chemotherapy. Cancer Med 2020; 9:5114-5123. [PMID: 32469145 PMCID: PMC7367625 DOI: 10.1002/cam4.3129] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 04/14/2020] [Accepted: 04/22/2020] [Indexed: 01/05/2023] Open
Abstract
Background The aim of this study was to assess chemotherapy‐induced polyneuropathy (CIPN) 5 years after adjuvant chemotherapy in patients with breast and colorectal cancer. The association of CIPN with quality of life, anxiety, and depression was analyzed. Methods Of a set of 100 patients with breast cancer and of 74 with colorectal cancer who had undergone surgery and adjuvant chemotherapy in 2011‐2012, 80 and 52 patients alive, respectively, were included together with two reference groups of 249 breast cancer patients and 83 colorectal cancer patients who had undergone surgery only. All patients were sent a questionnaire on alcohol consumption, smoking habits, comorbidity, medicine consumption, and oxaliplatin‐specific questions, as well as the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), the Douleur Neuropathique 4 Questions (DN4q), the EQ‐5D, and the Hospital Anxiety and Depression Scale. Possible polyneuropathy was defined as the presence of numbness and/or tingling in the feet, secondly as a score of ≥4 on the MNSIq. Possible painful polyneuropathy was defined as pain in both feet and a score ≥3 on the DN4q. Results The prevalence of possible polyneuropathy defined by numbness and/or tingling in the feet was 38.8% (28.1‐50.3) after adjuvant docetaxel and 57.7% (43.2‐71.3) after adjuvant oxaliplatin, with no significant difference from a previous 1‐year follow‐up (P >.35). Fewer had possible polyneuropathy as defined by the MNSIq. Patients with possible polyneuropathy after adjuvant chemotherapy reported significantly lower quality of life than patients treated with surgery only. Conclusion Symptoms of polyneuropathy following adjuvant docetaxel and oxaliplatin persist 5 years after treatment and affect quality of life negatively.
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Affiliation(s)
- Kristine Bennedsgaard
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Lise Ventzel
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Andreas C Themistocleous
- Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.,Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - David L Bennett
- Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK
| | - Anders B Jensen
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Anni R Jensen
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Niels T Andersen
- Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Troels S Jensen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
| | - Hatice Tankisi
- Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark
| | - Nanna B Finnerup
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
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Ballinger TJ, Cunningham GM, Wu X, Schneider BP. Impact of Genetic Ancestry on Treatment Toxicity and Racial Disparities in Breast Cancer. CURRENT BREAST CANCER REPORTS 2020. [DOI: 10.1007/s12609-020-00369-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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41
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Hwang MS, Lee HY, Choi TY, Lee JH, Ko YS, Jo DC, Do K, Lee JH, Park TY. A systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy. Medicine (Baltimore) 2020; 99:e19837. [PMID: 32332632 PMCID: PMC7220547 DOI: 10.1097/md.0000000000019837] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 02/23/2020] [Accepted: 03/10/2020] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) occurs in 68.1% of patients within the first month of undergoing chemotherapy; however, standardized treatment for CIPN has not been established yet. The efficacy of acupuncture, a widely used treatment for CIPN in South Korea, has not been studied sufficiently. This study aimed to review the studies that evaluated the efficacy of acupuncture or electroacupuncture (EA) in treating CIPN. METHODS A literature search was performed on relevant international databases - MEDLINE, Embase, the Allied and Complementary Medicine Databases, and China National Knowledge Infrastructure - as well as Korean databases - the National Digital Science Library, Oriental Medicine Advanced Searching Integrated System, DBpia, and Korean Studies Information Service System. Randomized controlled trials (RCTs) that aimed to treat CIPN symptoms with acupuncture or EA and set not only a control group with a conventional pharmacological treatment or injection, but also a placebo control or sham-acupuncture group, were included. Meta-analysis was conducted to elucidate the efficacy of acupuncture/EA on the basis of symptom score. RESULTS Of the 13 studies included in the literature review, 12 RCTs compared acupuncture and pharmacological treatments. There were 3 EA RCTs, but only 1 RCT compared EA and sham-EA. A total of 832 participants were included in these studies. Five RCTs showed that acupuncture was more effective than pharmacological treatment in terms of efficacy rate. Regarding the risk of bias summary, the quality of included studies was poor. Only 1 study compared the efficacy of EA and sham EA; therefore, the specific efficacy of acupuncture could not be elucidated. CONCLUSION Acupuncture is safe, but the symptom-alleviating effect on CIPN can hardly be determined because of methodological deficiencies of the included studies. In terms of the clinical efficacy rate, acupuncture was more effective than conventional pharmacological treatments. PROSPERO REGISTRATION NUMBER CRD42018111509.
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Affiliation(s)
- Man-Suk Hwang
- 3rd Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan
| | - Hye-Yoon Lee
- School of Korean Medicine, Pusan National University, Yangsan
| | - Tae-Young Choi
- Medical Research Division, Korea Institute of Oriental Medicine, Daejeon
| | - Jung-Han Lee
- Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Wonkwang University, Iksan
| | - Youn-Seok Ko
- Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Woo-Suk University, Jeonju, Jeonbuk
| | - Dong Chan Jo
- Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Woo-Suk University, Jeonju, Jeonbuk
| | - Kwangsun Do
- Institute for Integrative Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Jin-Hyun Lee
- Institute for Integrative Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
| | - Tae-Yong Park
- Institute for Integrative Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon, Republic of Korea
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Rosenbaek F, Holm HS, Hjelmborg JVB, Ewertz M, Jensen JD. Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer. Support Care Cancer 2019; 28:3763-3769. [PMID: 31828491 DOI: 10.1007/s00520-019-05196-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 11/20/2019] [Indexed: 01/09/2023]
Abstract
BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel. Though no pharmacological agents have been identified to prevent CIPN, cryotherapy with frozen gloves and socks may reduce the risk of developing CIPN and thereby increase the likelihood of patients completing the planned dose of paclitaxel. PATIENTS AND METHODS Among women with early-stage breast cancer who received at least one cycle of paclitaxel, 119 were included in the 2016 cohort who received cryotherapy when they developed symptoms of CIPN, and 96 patients in the 2017 cohort who received prophylactic cryotherapy. From electronic patient records, data were abstracted on dates and doses of adjuvant paclitaxel, dose reductions, cycle delays, symptoms of CIPN, and whether and when frozen gloves and socks were used. The outcome was the proportion of patients completing the planned 720 mg/m2 of paclitaxel cumulated over nine cycles. The hazard ratio (HR) of a dose-limiting event due to CIPN was estimated in a Cox proportional hazards model. RESULTS In the 2016 cohort, cryotherapy was needed due to symptoms of CIPN in 54 (45%) patients. Significantly, more patients, 77% in the 2017 cohort, completed the planned dose of 720 mg/m² compared with 64% in the 2016 cohort, p = 0.017. The HR of a dose reduction or cessation due to CIPN, adjusted for age and HER-2 status, was 0.50 (95% confidence interval 0.30-0.84), p = 0.009, for the 2017 cohort compared with the 2016 cohort. CONCLUSIONS The results of this study suggest that prophylactic cryotherapy may reduce the risk of a dose-limiting event due to CIPN and increase the proportion of patients completing the planned dose of paclitaxel in adjuvant treatment of early-stage breast cancer. Despite this, CIPN remains to be an important dose-limiting toxicity of paclitaxel.
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Affiliation(s)
- F Rosenbaek
- Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense, Denmark
- Institute of Clinical Research,University of Southern Denmark, Odense, Denmark
| | - H S Holm
- Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense, Denmark
| | - J V B Hjelmborg
- Department of Epidemiology and Biostatistics, University of Southern Denmark, Odense, Denmark
| | - M Ewertz
- Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense, Denmark
- Institute of Clinical Research,University of Southern Denmark, Odense, Denmark
| | - Jeanette Dupont Jensen
- Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, DK-5000, Odense, Denmark.
- OPEN, Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark.
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Saito M, Odajima S, Yokomizo R, Tabata J, Iida Y, Ueda K, Yanaihara N, Yamada K, Okamoto A. A simple method of quantifying chemotherapy-induced peripheral neuropathy using PainVision PS-2100 ®. Asia Pac J Clin Oncol 2019; 16:80-85. [PMID: 31774247 DOI: 10.1111/ajco.13293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 10/26/2019] [Indexed: 11/26/2022]
Abstract
AIM This study aimed to validate a simplified method of quantifying chemotherapy-induced peripheral neuropathy using the PainVision PS-2100® (PV) electrical perception system. METHODS We assessed patients diagnosed with epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer and were about to undergo first-time paclitaxel and carboplatin chemotherapy. Peripheral neuropathy was assessed before and after chemotherapy administration in all patients according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE4.0), using a conventional assessment in combination with the PV system. The PV device comprises electrodes attached to the ulnar side of the forearm and the first joint of index fingers on both the left and right sides to measure the electrical perceptual threshold. The average of three threshold measurements was recorded for each patient. RESULTS Thirty female patients (age 51.6 ± 12.2 [mean ± SD]) were included, and median number of chemotherapy drug treatments was 5 (first quartile: 4, second quartile: 5, and third quartile: 5). Twenty-seven patients (90%) reported posttreatment numbness; NCI-CTCAE4.0 perceptual anomaly grades were as follows: G1, 57 (40%); G2, 19 (13%); and G3, 7 (5%). A positive correlation was identified between right medial side PV threshold score and perceptual anomaly grade on measurements of the inner right-hand side only. CONCLUSION Our preliminary results suggest that peripheral neuropathy may be quantified using PV. As CIPN often lowers QOL, it needs to be appropriately evaluated. Future studies with a larger patient cohort and methodological refinements to improve accuracy are warranted.
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Affiliation(s)
- Motoaki Saito
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Suguru Odajima
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Ryo Yokomizo
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Jyunya Tabata
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasushi Iida
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kazu Ueda
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Nozomu Yanaihara
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Kyosuke Yamada
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
| | - Aikou Okamoto
- Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan
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Guillaumot MA, Cerles O, Bertrand HC, Benoit E, Nicco C, Chouzenoux S, Schmitt A, Batteux F, Policar C, Coriat R. Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator. Oncotarget 2019; 10:6418-6431. [PMID: 31741707 PMCID: PMC6849645 DOI: 10.18632/oncotarget.27248] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 09/10/2019] [Indexed: 01/09/2023] Open
Abstract
By using the differential in level of oxidative status between normal and cancer cells, SuperOxide Dismutase (SOD) mimetics can have anti-tumor efficacy and prevent oxaliplatin-induced peripheral neuropathy. Our objective was to evaluate the neuroprotective efficacy of MAG, a new SOD mimic. In vitro, the effects of MAG alone or with oxaliplatin were studied on colon cancer cells (HT29 and CT26) and on normal fibroblast cells (NIH3T3). The cell viability (by crystal violet) as well as the production of reactive forms of oxygen and glutathione (by spectrofluorimetric assay) was measured. In vivo, efficacy on tumor growth was assessed in mice grafted with CT26 colon cancer cells. The effects on induced neurotoxicity were measured by specific behavioral Von Frey nociception, cold-plate tests, specific functional neuromuscular assay and electron microscopy. In vitro, MAG induced a production of hydrogen peroxide in all cells. At 24 h-incubation, MAG exhibits a cytotoxic activity in all cell lines. A cytotoxic additive effect of MAG and oxaliplatin was observed through oxidative burst. In vivo, oxaliplatin-treated mice associated with MAG did not counteract oxaliplatin’s antitumoral efficacy. After 4 weeks of treatment with oxaliplatin combined with MAG, behavioral and functional tests showed a decrease in peripheral neuropathy induced by oxaliplatin in vivo. Electron microscopy analyses on sciatic nerves revealed an oxaliplatin-induced demyelination which is prevented by the association of MAG to this chemotherapy. In conclusion, MAG prevents the appearance of sensitive axonal neuropathy and neuromuscular disorders induced by oxaliplatin without affecting its antitumor activity.
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Affiliation(s)
- Marie-Anne Guillaumot
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France
| | - Olivier Cerles
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France
| | - Hélène C Bertrand
- Laboratoire des Biomolécules, LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France
| | - Evelyne Benoit
- Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), CEA de Saclay, Université Paris-Saclay, Gif-sur-Yvette, France.,Institut des Neurosciences Paris-Saclay (Neuro-PSI), CNRS, UMR CNRS/Université Paris-Sud 9197, Université Paris-Saclay, Gif-sur-Yvette, France
| | - Carole Nicco
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France
| | - Sandrine Chouzenoux
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France
| | - Alain Schmitt
- Plateforme Imagerie Cellulaire, Microscopie électronique Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, INSERM U1016, Paris, France
| | - Frédéric Batteux
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France.,Service d'Immunologie, Centre Hospitalo-Universitaire Cochin AP-HP, Université Paris Descartes, Paris, France
| | - Clotilde Policar
- Laboratoire des Biomolécules, LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, Paris, France
| | - Romain Coriat
- Département "Development, Reproduction and Cancer", Institut Cochin, Paris Descartes Université, Sorbonne Paris Cité, INSERM U1016, Paris, France.,Service de Gastro-Entérologie du Centre Hospitalo-Universitaire Cochin, APHP, Université Paris Descartes, Paris, France
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Spinal cord stimulation prevents paclitaxel-induced mechanical and cold hypersensitivity and modulates spinal gene expression in rats. Pain Rep 2019; 4:e785. [PMID: 31875188 PMCID: PMC6882571 DOI: 10.1097/pr9.0000000000000785] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 08/06/2019] [Accepted: 08/10/2019] [Indexed: 01/28/2023] Open
Abstract
Supplemental Digital Content is Available in the Text. Introduction: Paclitaxel-induced peripheral neuropathy (PIPN) is a common dose-limiting side effect of this cancer treatment drug. Spinal cord stimulation (SCS) has demonstrated efficacy for attenuating some neuropathic pain conditions. Objective: We aim to examine the inhibitory effect of SCS on the development of PIPN pain and changes of gene expression in the spinal cord in male rats after SCS. Methods: We examined whether traditional SCS (50 Hz, 6–8 h/session daily for 14 consecutive days) administered during paclitaxel treatment (1.5 mg/kg, i.p.) attenuates PIPN-related pain behavior. After SCS treatment, we performed RNA-seq of the lumbar spinal cord to examine which genes are differentially expressed after PIPN with and without SCS. Results: Compared to rats treated with paclitaxel alone (n = 7) or sham SCS (n = 6), SCS treatment (n = 11) significantly inhibited the development of paclitaxel-induced mechanical and cold hypersensitivity, without altering open-field exploratory behavior. RNA-seq showed that SCS induced upregulation of 836 genes and downregulation of 230 genes in the spinal cord of paclitaxel-treated rats (n = 3) as compared to sham SCS (n = 5). Spinal cord stimulation upregulated immune responses in paclitaxel-treated rats, including transcription of astrocyte- and microglial-related genes, but repressed transcription of multiple gene networks associated with synapse transmission, neuron projection development, γ-aminobutyric acid reuptake, and neuronal plasticity. Conclusion: Our findings suggest that traditional SCS may attenuate the development of pain-related behaviors in PIPN rats, possibly by causing aggregate inhibition of synaptic plasticity through upregulation and downregulation of gene networks in the spinal cord.
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Raphael M, Wei X, Karim S, Robinson A, Bedard P, Booth C. Neurotoxicity Among Survivors of Testicular Cancer: A Population-based Study. Clin Oncol (R Coll Radiol) 2019; 31:653-658. [DOI: 10.1016/j.clon.2019.04.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 11/16/2022]
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Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain. Int J Mol Sci 2019; 20:ijms20122904. [PMID: 31197114 PMCID: PMC6627296 DOI: 10.3390/ijms20122904] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 06/10/2019] [Accepted: 06/12/2019] [Indexed: 12/17/2022] Open
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of chemotherapics such as taxanes, vinca alkaloids, and platinum compounds. In recent years, several reports have indicated the involvement of different molecular mechanisms in CIPN. The pathways described so far are diverse and target various components of the peripheral Nervous System (PNS). Among the contributors to neuropathic pain, inflammation has been indicated as a powerful driver of CIPN. Several pieces of evidence have demonstrated a chemotherapy-induced increase in peripheral pro-inflammatory cytokines and a strong correlation with peripheral neuropathy. At present, there are not adequate strategies to prevent CIPN, although there are drugs for treating CIPN, such as duloxetine, that have displayed a moderate effect on CIPN. In this review, we focus on the players involved in CIPN with a particular emphasis on chemokine signaling.
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Bravo-Caparrós I, Perazzoli G, Yeste S, Cikes D, Baeyens JM, Cobos EJ, Nieto FR. Sigma-1 Receptor Inhibition Reduces Neuropathic Pain Induced by Partial Sciatic Nerve Transection in Mice by Opioid-Dependent and -Independent Mechanisms. Front Pharmacol 2019; 10:613. [PMID: 31263413 PMCID: PMC6584826 DOI: 10.3389/fphar.2019.00613] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Accepted: 05/15/2019] [Indexed: 12/12/2022] Open
Abstract
Sigma-1 (σ1) receptor antagonists are promising tools for neuropathic pain treatment, but it is unknown whether σ1 receptor inhibition ameliorates the neuropathic signs induced by nerve transection, in which the pathophysiological mechanisms and response to drug treatment differ from other neuropathic pain models. In addition, σ1 antagonism ameliorates inflammatory pain through modulation of the endogenous opioid system, but it is unknown whether this occurs during neuropathic pain. We investigated the effect of σ1 inhibition on the painful hypersensitivity associated with the spared nerve injury (SNI) model in mice. Wild-type (WT) mice developed prominent cold (acetone test), mechanical (von Frey test), and heat hypersensitivity (Hargreaves test) after SNI. σ1 receptor knockout (ခσ1-KO) mice did not develop cold allodynia and showed significantly less mechanical allodynia, although they developed heat hyperalgesia after SNI. The systemic acute administration of the selective σ1 receptor antagonist S1RA attenuated all three types of SNI-induced hypersensitivity in WT mice. These ameliorative effects of S1RA were reversed by the administration of the σ1 agonist PRE-084, and were absent in σ1-KO mice, indicating the selectivity of S1RA-induced effects. The opioid antagonist naloxone and its peripherally restricted analog naloxone methiodide prevented S1RA-induced effects in mechanical and heat hypersensitivity, but not in cold allodynia, indicating that opioid-dependent and -independent mechanisms are involved in the effects of this σ1 antagonist. The repeated administration of S1RA twice a day during 10 days reduced SNI-induced cold, mechanical, and heat hypersensitivity without inducing analgesic tolerance during treatment. These effects were observed up to 12 h after the last administration, when S1RA was undetectable in plasma or brain, indicating long-lasting pharmacodynamic effects. These data suggest that σ1 antagonism may have therapeutic value for the treatment of neuropathic pain induced by the transection of peripheral nerves.
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Affiliation(s)
- Inmaculada Bravo-Caparrós
- Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain.,Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.,Biosanitary Research Institute, University Hospital Complex of Granada, Granada, Spain
| | - Gloria Perazzoli
- Biosanitary Research Institute, University Hospital Complex of Granada, Granada, Spain.,Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada, Spain
| | - Sandra Yeste
- Drug Discovery and Preclinical Development, Esteve, Barcelona, Spain
| | - Domagoj Cikes
- Institute of Molecular Biotechnology, Vienna, Austria
| | - José Manuel Baeyens
- Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain.,Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.,Biosanitary Research Institute, University Hospital Complex of Granada, Granada, Spain
| | - Enrique José Cobos
- Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain.,Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.,Biosanitary Research Institute, University Hospital Complex of Granada, Granada, Spain.,Teófilo Hernando Institute for Drug Discovery, Madrid, Spain
| | - Francisco Rafael Nieto
- Department of Pharmacology, School of Medicine, University of Granada, Granada, Spain.,Institute of Neuroscience, Biomedical Research Center, University of Granada, Granada, Spain.,Biosanitary Research Institute, University Hospital Complex of Granada, Granada, Spain
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Li D, Lee JH, Choi CW, Kim J, Kim SK, Kim W. The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice. Int J Mol Sci 2019; 20:ijms20071652. [PMID: 30987090 PMCID: PMC6479607 DOI: 10.3390/ijms20071652] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 03/16/2019] [Accepted: 03/28/2019] [Indexed: 02/02/2023] Open
Abstract
The analgesic effect of venlafaxine (VLX), which is a selective serotonin and noradrenaline reuptake inhibitor (SNRI), has been observed on oxaliplatin-induced neuropathic pain in mice. Significant allodynia was shown after oxaliplatin treatment (6 mg/kg, i.p.); acetone and von Frey hair tests were used to assess cold and mechanical allodynia, respectively. Intraperitoneal administration of VLX at 40 and 60 mg/kg, but not 10 mg/kg, significantly alleviated these allodynia. Noradrenaline depletion by pretreatment of N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg, i.p.) blocked the relieving effect of VLX (40 mg/kg, i.p.) on cold and mechanical allodynia. However, serotonin depletion by three consecutive pretreatments of para-chlorophenylalanine (PCPA, 150 mg/kg/day, i.p.) only blocked the effect of VLX on mechanical allodynia. In cold allodynia, the α2-adrenergic antagonist idazoxan (10 μg, i.t.), but not the α1-adrenergic antagonist prazosin (10 μg, i.t.), abolished VLX-induced analgesia. Furthermore, idazoxan and 5-HT3 receptor antagonist bemesetron (MDL-72222, 15 μg, i.t.), but not prazosin or mixed 5-HT1, 2 receptor antagonist methysergide (10 μg, i.t.), abolished VLX-induced analgesia in mechanical allodynia. In conclusion, 40 mg/kg of VLX treatment has a potent relieving effect against oxaliplatin-induced neuropathic pain, and α2-adrenergic receptor, and both α2-adrenergic and 5-HT3 receptors are involved in this effect of VLX on cold and mechanical allodynia, respectively.
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Affiliation(s)
- Daxian Li
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
| | - Ji Hwan Lee
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
| | - Chang Won Choi
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
| | - Jaihwan Kim
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
| | - Sun Kwang Kim
- Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
| | - Woojin Kim
- Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea.
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
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Hwang MS, Lee HY, Lee JH, Choi TY, Lee JH, Ko YS, Choi SY, Park TY. Protocol for a systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy. Medicine (Baltimore) 2019; 98:e15098. [PMID: 30946370 PMCID: PMC6456145 DOI: 10.1097/md.0000000000015098] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 30% to 40% of patients who receive chemotherapy; however, standardized treatment for CIPN has not yet been developed. Acupuncture is widely used to treat CIPN in Korea, but its efficacy has not been investigated. The purpose of this study is to review the current literature on the efficacy of acupuncture and electroacupuncture (EA) in treating CIPN. MATERIALS AND METHODS We will perform a literature review using the relevant databases, including MEDLINE, Embase, the Allied and Complementary Medicine Databases (AMED), and China National Knowledge Infrastructure (CNKI), as well as Korean databases, including the National Digital Science Library (NDSL), Oriental Medicine Advanced Searching Integrated System (OASIS), DBpia, and Korean studies Information Service System (KISS). Randomized controlled trials describing treatment of CIPN symptoms with acupuncture or EA will be included. The primary outcomes will be scores on a visual analog scale and a numeric rating scale for neuropathic pain. We will also assess the risk of bias by evaluating the available studies using the tools of the Cochrane Collaboration and carry out a meta-analysis. ETHICS AND DISSEMINATION Ethical approvals and patient consent are not necessary because the meta-analysis will be based on published research. We will submit our meta-analysis to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER CRD42018111509.
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Affiliation(s)
- Man-Suk Hwang
- Third Division of Clinical Medicine, School of Korean Medicine, Pusan National University
| | - Hye-Yoon Lee
- National Clinical Research Center for Korean Medicine, Pusan National University Korean Medicine Hospital, Yangsan
| | - Jin-Hyun Lee
- Institute for Integrative Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon
| | - Tae-Young Choi
- Medical Research Division, Korea Institute of Oriental Medicine, Daejeon
| | - Jung-Han Lee
- Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Wonkwang University, Iksan
| | - Youn-Seok Ko
- Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Woo-Suk University, Jeonju, Jeonbuk
| | - Sung-Youl Choi
- Department of Neuropsychiatry, College of Korean Medicine, Gachon University, Seongnam, Gyeonggi, Republic of Korea
| | - Tae-Yong Park
- Institute for Integrative Medicine, Catholic Kwandong University International St. Mary's Hospital, Incheon
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