Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.078
Filtrar
1.
Medicine (Baltimore) ; 99(3): e18830, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011497

RESUMO

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects of chemotherapy. Its main symptoms are pain, paresthesia, and numbness. However, the mechanisms underlying the development of CIPN remain unclear and standard treatments have not been established. Recently, there has been a growing interest in various approaches to overcome the limitations of the existing treatments. This study aims to evaluate the efficacy and safety of the concurrent use of two complementary and alternative therapies: electroacupuncture (EA) and Chuna manual therapy (CMT), with pregabalin, which is the conventional pharmacotherapy for neuropathic pain. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial, which includes 90 patients with colorectal and breast cancer, who developed CIPN. After a 2-week preparation period, the patients are divided into three groups (pregabalin administration group, pregabalin + EA treatment group, and pregabalin + CMT treatment group), treated for approximately 5 weeks and followed-up 4 weeks after treatment. The primary outcome is assessed using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity subscale score (version 4.0) and the secondary outcome is measured using the Quality of Life Questionnaire-CIPN 20-Item Scale (version 3.0) and the quality of life questionnaire (version 3.0) developed by the European Organisation for Research and Treatment of Cancer. Moreover, exploratory efficacy and safety evaluations will be conducted based on the chemotherapy-completion rate and nerve conduction studies.


Assuntos
Terapia por Acupuntura , Analgésicos/uso terapêutico , Antineoplásicos/efeitos adversos , Manipulações Musculoesqueléticas , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Pregabalina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Projetos de Pesquisa
2.
Medicine (Baltimore) ; 99(6): e19029, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028414

RESUMO

When the 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy regimen is used to treat colorectal cancer (CRC), chemotherapy-induced peripheral neuropathy (CIPN) caused by oxaliplatin can substantially affect quality of life (QOL) in the CRC patients. This study compared emotional distress and QOL during FOLFOX in CRC patients with and without CIPN symptoms.This cross-sectional, descriptive, and comparative study recruited 68 CRC patients receiving FOLFOX at a local teaching hospital and at a medical center in southern Taiwan. Self-reported structured questionnaires (oxaliplatin-associated neuropathy questionnaire, profile of mood states short form, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30, version 3.0) were used for 1-time data collection. The Chi-square test, Fisher exact test, and Mann-Whitney U test were used to analyze data, and a P-value < .05 was considered statistically significant.The CIPN group had 45 (66.2%) patients, and the non-CIPN group had 23 (33.8%) patients. The 5 most common symptoms were coldness-related burning sensation or discomfort in the upper limbs, numbness in the upper limbs, tingling in the upper limbs, impairment of vision, and discomfort in the throat. The CIPN group had more females (P = .013), a more advanced stage of CRC (P = .04) and a higher chemotherapy dosage (P = .006). The 2 groups did not significantly differ in anxiety (P = .065) or depression (P = .135). Compared to the non-CIPN group, the CIPN group had significantly lower functioning (P = .001) and global health status (P < .001) and significantly more symptoms (P < .001).The CIPN group had significantly lower QOL compared to the non-CIPN group. However, the CIPN group did not have lower emotional distress compared to the non-CIPN group. The results of this study demonstrate the need for in-service courses specifically designed to train health professionals in assessing and managing CIPN symptoms to improve QOL in CRC patients receiving FOLFOX.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Qualidade de Vida , Estresse Psicológico/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/psicologia , Estudos Transversais , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Doenças do Sistema Nervoso Periférico/psicologia , Estresse Psicológico/etiologia , Inquéritos e Questionários
3.
Artigo em Chinês | MEDLINE | ID: mdl-32062896

RESUMO

Objective: To investigate the clinical manifestations, electrophysiology results, treatment and prognosis of acrylamide-induced toxic peripheral neuropathy. Methods: The clinical data of 9 patients with acrylamide-induced toxic peripheral neuropathy, who were collected in Jinhua Municipal Central Hospital from January 2015 to August 2018, were retrospectively reviewed. Results: This disease was characterized by distal limb numbness, some patients with hypoalgesia or allergy, deep sense loss, reduction or disappearance of tendon reflexes, and peeling. One case had muscle weakening and another case had cerebellar ataxia. Examination of electromyography showed only one case had spontaneous potential. Examination of nerve conduction showed that the amplitude decreased by 34 (38.6%) and the velocity decreased by 2 (2.3%) , the percentage of amplitude decreased was significantly higher than that of velocity decreased. The amplitude of sensory nerve decreased by 30 (57.7%) and motor nerve decreased by 4 (11.1%) , the percentage of sensory nerve amplitude decreased was significantly higher than that of motor nerve. After the treatment of nutrition, circulation improvement, numbness relief, glucocorticoid and other drugs, the numbness of the patients was relieved, but it did not completely disappear. Poor recovery of pain, deep sensation and tendon reflex in all patients. The results of reexamination of electromyography in 3 cases were worse than before. Therefore, it is suggested that peripheral nerve damage is irreversible. Conclusion: This disease is characterized by distal limb numbness. Electrophysiological results suggest that the damage of sensory nerve axon is the main cause of the disease. Up to now, there is no effective drug to treat this disease, therefore, it is very important to do a good job of protection.


Assuntos
Acrilamida/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , China , Eletromiografia , Humanos , Condução Nervosa , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 99(1): e18653, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895829

RESUMO

BACKGROUND: To compare the efficacy of serotonin-norepinephrine reuptake inhibitors (SNRIs) treatment for chemotherapy-induced peripheral neuropathy (CIPN) METHODS:: Two authors independently searched MEDLINE, Embase, Cochran Library, and Web of Science to identify and review articles published from January 1998 until December 2018 according to selection criteria. Outcomes were expressed as mean difference, the pooled odds ratio, or relative risk in a meta-analysis model. RESULTS: A total of 10 studies were included in this meta-analysis: 6 randomized-controlled studies and 4 observational studies. Meta-analysis showed that CIPN was improved after treatment with SNRI (standardized mean difference = 2.20; 95% confidence interval, 0.90-3.49; I = 93% in 3 randomized controlled studies). Somnolence and insomnia occurred in <15% of patients. Incidence of somnolence was lower than with pregabalin treatment, and insomnia was comparable to that in expectant management or pregabalin treatment. Incidence of nausea and vomiting was higher than in expectant management, but no significant difference was found when compared to expectant management. CONCLUSION: From the several available studies suitable for indirect comparison, SNRI shows excellent efficacy and tolerability to CIPN. SNRI could provide an important treatment option for CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente
5.
Chem Biol Interact ; 317: 108961, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31978392

RESUMO

Cisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients. Although considered to be life-saving as a cancer treatment, Pt-based drugs frequently result in dose-limiting toxicities such as chemotherapy-induced peripheral neuropathies (CIPN). Specifically, irreversible damage to outer hair cells and injury of sensory neurons are linked to profound sensorineural hearing loss (ototoxicity), which complicates tumor management and can lead to a poor clinical prognosis. Given the severity of CIPN, substantial effort has been devoted to the development of neuroprotective compounds, regardless clinical results have been underwhelming. It is noteworthy that Pt is a highly reactive electrophile (electron deficient) that causes toxicity by forming adducts with nucleophilic (electron rich) targets on macromolecules. In this regard, we have discovered a series of carbon-based enol nucleophiles; e.g., N-(4-acetyl-3,5-dihydroxyphenyl)-2-oxocytclopentane-1-carboxamide (Gavinol), that can prevent neurotoxicity by scavenging the platinum ion. The chemistry of enol compounds is well understood and mechanistic research has demonstrated the role of this chemistry in cytoprotection. Our cell-derived data were corroborated by calculations of hard and soft, acids and bases (HSAB) parameters that describe the electronic character of interacting electrophiles and nucleophiles. Together, these observations indicate that the respective mechanisms of Pt neurotoxicity and antitumor activity are separable and can therefore be affected independently.


Assuntos
Antineoplásicos/efeitos adversos , Síndromes Neurotóxicas , Compostos Organoplatínicos/toxicidade , Platina/toxicidade , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Ratos
6.
Chem Biol Interact ; 315: 108906, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31760042

RESUMO

The microtubule inhibitor (MTI) class of chemotherapeutics provide an effective treatment for several different types of cancers, however, severe chemotherapy-induced peripheral neuropathy (CIPN) is a major dose limiting toxicity in patients that limits their use. While CIPN was predicted with MTIs based on histopathology and functional effects in non-clinical toxicology studies, these investigations often require large numbers of animals and long term studies. As in vitro MT assays have been used for decades to study mechanisms of efficacy, we hypothesized that those same assays could be used to study mechanisms of peripheral neuropathy and predict severe CIPN. We analyzed published data on in vitro microtubule (MT) properties for different MTIs that cause varying levels of peripheral neuropathy in patients. Eribulin, vinorelbine and vinfluinine, which all have less severe CIPN than the vinca alkaloids or taxanes, have unique MT properties consisting of reduced affinity and limited binding to MTs (i.e. bind only to the ends and not along the length). Binding more potently to tubulin in the absence of neuronal BIII tubulin was also observed with eribulin and may suggest specificity for tumor tubulin over neuronal tubulin. These are possible mechanisms for causing less severe deleterious effects on MTs in peripheral nerves leading to reduced severity of CIPN. Our analyses demonstrated that in vitro tools used to study the mechanisms of action in inducing severe CIPN (i.e MTI interactions with MTs) warrant further investigation and may be useful for developing next generation MTIs with reduced CIPN.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Microtúbulos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Moduladores de Tubulina/efeitos adversos , Moduladores de Tubulina/uso terapêutico , Animais , Humanos , Microtúbulos/metabolismo , Neoplasias/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Tubulina (Proteína)/metabolismo
7.
Crit Rev Oncol Hematol ; 145: 102831, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31783290

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of chemotherapy that is frequently experienced by patients receiving treatment for cancer. CIPN is caused by many of the most commonly used chemotherapeutic agents, including taxanes, vinca alkaloids, and bortezomib. Pain and sensory abnormalities may persist for months, or even years after the cessation of chemotherapy. The management of CIPN is a significant challenge, as it is not possible to predict which patients will develop symptoms, the timing for the appearance of symptoms can develop anytime during the chemotherapy course, there are no early indications that warrant a reduction in the dosage to halt CIPN progression, and there are no drugs approved to prevent or alleviate CIPN. This review focuses on the etiology of CIPN and will highlight the various approaches developed for prevention and treatment. The goal is to guide studies to identify, test, and standardize approaches for managing CIPN.


Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Bortezomib/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Taxoides/uso terapêutico
8.
Life Sci ; 244: 117095, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816326

RESUMO

AIMS: Investigate Melatonin administration along with Vincristine (VCR) owing to two reasons: First, Melatonin's sciatic nerve protective effect against Chemotherapy Induced Peripheral Neuropathy (CIPN). Second, Vincristine's anticancer work potentiation that may lead to a decrease in its dose and its side effects accordingly. MAIN METHODS: In vivo and in vitro experiments were conducted in the study. The in vivo experiment included developing a CIPN Wistar Albino rat model. They were injected with VCR sulfate to induce CIPN, while Melatonin and Pregabalin (neuroleptic) were co-administered with the aim of investigating the degeneration/protection of the sciatic nerve. Tail Immersion Test and histopathological analyses were done to validate the experimental model (induction of rat peripheral neurodegeneration) and examine the possible Melatonin and Pregabalin protective/analgesic effects respectively. Liver and kidney function tests, catalase activity and malondialdehyde (MDA) level were measured. Concerning the in vitro experiment, cell viability assays in addition to ELISA (for caspases 3&9) were conducted using HCT-116 colon cancer cell line treated with VCR, Melatonin and their combination. KEY FINDINGS: VCR caused an elevated level of oxidation (MDA level increment) in the sciatic nerve, while Melatonin could prove its antioxidant effect through increasing catalase activity (antioxidant enzyme) with no significant toxic effect on body's functions. HCT-116 in vitro test proved the strong cytotoxic effect of VCR in addition to the synergistic effect of combining Melatonin to VCR on the cellular apoptotic level (caspases 3&9 increased activity levels) and inhibitory concentration 50%. SIGNIFICANCE: Melatonin possesses an antioxidant property that can protect the sciatic nerve from CIPN-induced degeneration and potentiate VCR's anticancer effect at the same time.


Assuntos
Sinergismo Farmacológico , Melatonina/uso terapêutico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Pregabalina/uso terapêutico , Vincristina/toxicidade , Animais , Anticonvulsivantes/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/uso terapêutico , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Ratos , Ratos Wistar
9.
Lancet ; 394(10214): 2084-2095, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31791688

RESUMO

BACKGROUND: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer. METHODS: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3). FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0-26·0] in group 1, 24·9 months [24·0-25·9] in group 2, 25·3 months [23·9-26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6-not reached] in group 1, 20·8 months [11·9-59·0] in group 2, 21·0 months [12·0-54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups. INTERPRETATION: Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Grupo com Ancestrais do Continente Asiático , Carboplatina/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Carcinoma Epitelial do Ovário/patologia , Quimioterapia Adjuvante , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Procedimentos Cirúrgicos de Citorredução , Grupo com Ancestrais do Continente Europeu , Neoplasias das Tubas Uterinas/patologia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Neoplasias Peritoneais/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais
10.
Adv Exp Med Biol ; 1190: 357-369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760656

RESUMO

A large variety of drugs have been reported to cause peripheral neuropathies as dose-limiting adverse effects; however, most of them primarily affect axons and/or neuronal cell bodies rather than Schwann cells and/or myelin sheaths. In this chapter, we focus on the drugs that seem to elicit the neuropathies with schwannopathy and/or myelinopathy-predominant phenotypes, such as amiodarone, dichloroacetate, and tumor necrosis factor-α antagonists. Although the pathogenesis of demyelination induced by these drugs remain largely obscure, the recent in vivo and in vitro studies have implicated the involvement of metabolic abnormalities and impaired autophagy in Schwann cells and immune system disorders in the disruption of neuron-Schwann cell contact and interactions.


Assuntos
Doenças Desmielinizantes/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bainha de Mielina/patologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Células de Schwann/patologia , Amiodarona/efeitos adversos , Axônios , Ácido Dicloroacético/efeitos adversos , Humanos , Bainha de Mielina/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores
11.
Nihon Yakurigaku Zasshi ; 154(5): 236-240, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735750

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) considerably impairs cancer patients' QOL, and may lead to discontinuation of drug treatment of cancer. Currently, there is no effective strategy against CIPN. Therefore, it is an urgent issue to develop clinically available drugs that prevent or treat CIPN. We have shown that high mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, plays an essential role in the development of CIPN. Most interestingly, thrombomodulin α, approved as a medicine for treatment of disseminated intravascular coagulation (DIC) in Japan, causes thrombin-dependent degradation of extracellular HMGB1 that is released in response to chemotherapeutics, and prevents CIPN. Thus, we expect that targeting HMGB1 or its receptors would lead to prevention of CIPN in cancer patients in near future.


Assuntos
Antineoplásicos/efeitos adversos , Proteína HMGB1 , Terapia de Alvo Molecular , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Trombomodulina/uso terapêutico , Humanos , Japão , Doenças do Sistema Nervoso Periférico/prevenção & controle
12.
Nihon Yakurigaku Zasshi ; 154(5): 241-244, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735751

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect frequently caused by taxanes. Because the mechanisms underlying CIPN pathogenesis remain to be fully elucidated, there is no indicator for objective diagnosis like a biomarker. In addition, treatment options for CIPN is still unsatisfactory. We have previously demonstrated that paclitaxel preferentially impair myelin-forming Schwann cells, and consequently induce dedifferentiation and demyelination of Schwann cells. Recently, in a paclitaxel CIPN model mouse, we found that an inflammatory factor is released from dedifferentiated Schwann cells in the mouse sciatic nerve into the blood, highly correlated with the on-set of mechanical hypersensitivity. On the other hand, considering our previous findings, it seems that some drugs, which supply newly formed mature Schwann cells at the sites of demyelinated lesions, may be a new beneficial therapy for taxane-induced peripheral neuropathy. In this review, we will introduce our findings about new therapeutic drug candidate for taxane-related CIPN based on this concept, and plasma biomarker to detect CIPN on-set and progression.


Assuntos
Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/terapia , Taxoides/efeitos adversos , Animais , Biomarcadores , Camundongos , Células de Schwann/efeitos dos fármacos
13.
Nihon Yakurigaku Zasshi ; 154(5): 245-248, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31735752

RESUMO

Chemotherapy induced peripheral neuropathy (CIPN) is a numbness or tingling of the hands and feet that occur as a side effect of anticancer drugs including taxanes and platinum drugs. The effective treatments or preventive strategy are not established. Once it develops, symptoms persist for a long time and cause impairment in activity of daily living. Topical cooling is a preventive strategy for side effects of chemotherapy such as hair loss, oral microsites, and skin and nail disorder of the hands and feet. We conducted a clinical trial in breast cancer patients who received paclitaxel treatment to assess the effectiveness of cooling for CIPN prevention. In this study, the individual background factor was standardized using an intra-individual comparison design. In 40 subjects, frozen gloves and socks were applied on the dominant hand and foot from 15 minutes before the anti-cancer drug administration to 15 minutes after the end of administration (total 90 minutes) and compared with non-dominant hand and foot. As a result, clinically and statistically significant differences were observed for changes in tactile threshold evaluated by the monofilament test, subjective symptoms, and changes in dexterity evaluated by functional test. The current cooling system has not been well implemented in oncology field due to the lack of facility and human resources. To deliver this therapy broadly, it will be urgent to develop a medical cooling device that can provide safe and effective cryotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Crioterapia , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/terapia , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Doenças do Sistema Nervoso Periférico/induzido quimicamente
14.
Turk Neurosurg ; 29(6): 901-908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573061

RESUMO

AIM: To evaluate the effects of agomelatine on the biochemical and pathological features of cisplatin-induced peripheral neuropathy. MATERIAL AND METHODS: This study included a total of 30 male Wistar albino rats that weighed 285â€"300 grams and were divided into three groups: healthy controls (HC, n=10); cisplatin group (CIS, n=10) and agomelatine plus cisplatin group (AC, n=10). The CIS group received only cisplatin (EbeweLiba, Turkey) at a dose of 2.5 mg/kg, whereas the AC group received both agomelatine (25 mg/kg, Les Laboratoires Servier, France) and cisplatin (2.5 mg/kg). The animals were sacrificed by thiopental anaesthesia (50 mg/ kg, IE Ulagay, Turkey) and sciatic nerves were dissected. The sciatic nerve tissue was analysed for the levels of malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH) and superoxide dismutase (SOD) and was examined histopathologically. RESULTS: The mean levels of MDA, MPO, tGSH and SOD were 34.90 ± 13.83, 41.30 ± 18.03, 15.40 ± 6.06 and 48.60 ± 18.19, respectively. MDA and MPO were significantly lower in the AC group than in the CIS group (p < 0.001 for both). However, the antioxidative parameters tGSH and SOD were significantly higher in the AC group than in the CIS group (p < 0.001 for both). Pathological examinations revealed swollen myelinated nerve fibres and evident myelin sheath degeneration in the CIS group; in the AC group, the myelin sheath degeneration was less and the blood vessels were normal. CONCLUSION: Agomelatine decreased the oxidative status in an experimental rat model of cisplatin-induced peripheral neuropathy. Myelin sheath degeneration was less in the AC group than in the CIS group. To our knowledge, this was the first study that showed the positive effects of agomelatine on cisplatin-induced neuropathy in rats.


Assuntos
Acetamidas/uso terapêutico , Antineoplásicos/toxicidade , Antioxidantes/uso terapêutico , Cisplatino/toxicidade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Acetamidas/farmacologia , Animais , Antioxidantes/farmacologia , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Doenças do Sistema Nervoso Periférico/metabolismo , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo
15.
BMC Cancer ; 19(1): 941, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604467

RESUMO

BACKGROUND: Paclitaxel is used in second-line conventional chemotherapies to manage patients with unresectable advanced gastric cancer (GC). Paclitaxel-induced peripheral neuropathy is a known adverse event leading to treatment discontinuation. Additionally, oxaliplatin which causes irreversible peripheral neuropathy is now commonly used in first-line chemotherapy for advanced GC in Japan. Thus, examining the incidence of peripheral neuropathy with paclitaxel after oxaliplatin is necessary to improve the quality of life and outcomes of patients with advanced GC in the second-line treatment setting. METHODS: This prospective observational multicenter study, (which we named IVY study), will evaluate the degree of chemotherapy-induced peripheral neuropathy (CIPN) and the efficacy of second-line chemotherapy for unresectable advanced GC. A patient neurotoxicity questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) will be used to assess CIPN during the second-line treatment. The key eligibility criteria are as follows: 1) unresectable or recurrent GC histologically confirmed to be primary adenocarcinoma of the stomach, 2) age over 20 years, 3) Eastern Cooperative Oncology Group performance status score of 0-2, 4) written informed consent following full study information is provided to the patient, 5) progression or intolerance for first-line chemotherapy comprising fluorinated pyrimidine and platinum anticancer drugs (cisplatin or oxaliplatin) for advanced GC. 6) presence of evaluable lesions as confirmed using a computed tomography (CT) or magnetic resonance imaging. A total of 200 patients is considered to be appropriate for inclusion in this study. DISCUSSION: The results of this study will provide some information on CIPN with the sequential usage of oxaliplatin as first-line chemotherapy to paclitaxel as second-line chemotherapy in clinical practice. TRIAL REGISTRATION: This trial is registered in the University Hospital Medical Information Network's Clinical Trials Registry with the registration number UMIN000033376 (Registered 11 July 2018).


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Paclitaxel/uso terapêutico , Doenças do Sistema Nervoso Periférico/epidemiologia , Neoplasias Gástricas/tratamento farmacológico , Administração Intravenosa , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Japão , Oxaliplatina/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1654-1663, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607328

RESUMO

OBJECTIVE: To compare the effects of intravenous and subcutaneous injection of bortezomib on incidence and relative risk of peripheral neuropathy in patients with multiple myeloma(MM). METHODS: The electronic database of PubMed, Embase, Cochrance library, CNKI and related meeting records were searched by computers. The data were derived all from a matched randomized controlled studies. The incidence, relative risk(RR) and 95% confidence interval of peripheral neuropathy caused by intravenous and subcustaneous injections were calculated by the statistical methods. RESULTS: Four RCT studies were selected for meta-analysis, with a total of 911 patients (479 cases and 432 cases in the subcutaneous injection and intravenous injection groups, respectively). The incidence of peripheral neuropathy in the intravenous injection group was 41.4% (95% CI=0.137-0.692, P=0.003), and the incidence of >2 grade of peripheral neuropathy was 15.6% (95% CI=0.005-0.308, P=0.043). The corresponding incidence rates of the subcutaneous injection group were 16% (95% CI=0.021-0.299, P=0.024) and 3.4% (95% CI=-0.011-0.080, P=0.141) respectively. Compared with the intravenous injection group, the RR of peripheral neuropathy and the relative risk of peripheral neuropathy above grade 2 were 0.525, 95% CI=0.297-0.928 (P=0.027) and 0.376, 95% CI=0.196-0.722 (P=0.003) respectively. CONCLUSION: Subcutaneous injection of bortezomib at therapeutic doses significantly reduces the incidence of peripheral neuropathy compared with intravenous injection.


Assuntos
Bortezomib/efeitos adversos , Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Antineoplásicos , Humanos , Incidência , Injeções Subcutâneas , Doenças do Sistema Nervoso Periférico/induzido quimicamente
17.
BMC Cancer ; 19(1): 904, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506070

RESUMO

BACKGROUND: Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity. METHODS: We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α. RESULTS: Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity. CONCLUSIONS: The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.


Assuntos
Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico
18.
Eur J Oncol Nurs ; 42: 82-89, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473465

RESUMO

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) can interfere with activities of daily living and can negatively affect symptoms. Thus, this study aimed to develop and implement an aroma self-foot reflexology regimen based on Cox's Interaction Model of Client Health Behaviour (IMCHB) as an intervention that can be self-performed at home and at any time. The effects of aroma self-foot reflexology on peripheral neuropathy, peripheral skin temperature, anxiety, and depression were examined in patients with gynaecologic cancer who were undergoing chemotherapy. METHODS: This randomized controlled trial included 32 experimental and 31 control patients with CIPN. Data were collected using self-reported questionnaires (CIPN assessment tool, HADS). In the experimental group, peripheral neuropathy, peripheral skin temperature, anxiety, and depression were measured before and after aroma self-foot reflexology therapy for 6 weeks. The control group was provided with identical aroma self-foot reflexology training 6 weeks later and underwent the intervention at that time. RESULTS: The intervention resulted in lower levels of symptoms of peripheral neuropathy, less interference with activities (p < .001), and higher peripheral skin temperature level (p < .001). Anxiety and depression decreased in the experimental group (p < .001). The ratio of borderline and definite cases of anxiety and depression did not differ between groups. CONCLUSIONS: An aroma self-foot reflexology intervention can reduce CIPN, anxiety, and depression in gynaecologic cancer patients. Further research is required to assess the effects of differences in the content of the intervention and the effects of various numbers of applications and durations of applications based on each individual patient's condition.


Assuntos
Ansiedade/terapia , Depressão/terapia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Manipulações Musculoesqueléticas/métodos , Doenças do Sistema Nervoso Periférico/terapia , Temperatura Cutânea , Atividades Cotidianas , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/diagnóstico , Depressão/etiologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/psicologia , Humanos , Massagem , Pessoa de Meia-Idade , Odorantes , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/psicologia , Inquéritos e Questionários
19.
Biomed Res Int ; 2019: 5347804, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380428

RESUMO

Chemotherapy induced peripheral neuropathy (CIPN) is a serious adverse effect of chemotherapeutics with limited pathogenetic mechanism been known. Whether microcirculatory disturbance is involved in CIPN has not been reported. Considering that tissue factor (TF) is an endogenous coagulation factor, we hypothesize CIPN may be induced by the high expression of TF in macrophages and sciatic nerve, which induces the molecular signal related to ischemia and hypoxia. Oxaliplatin (L-OHP) was used to establish CIPN model. Von Frey Hairs was used to measure nociception. The murine macrophage cell line Raw 264.7 was used for cell experiments. Gelatin zymography and western blotting were used to measure the activity or expression of protein. TF expression and MMP-9/2 activity in sciatic nerve and blood are significantly increased by L-OHP. L-OHP increased the release of HSP70 from macrophage and enhanced the expression of p-p38 and HIF-1α in vivo and in vitro. Hirudin significantly suppressed the overexpression of p38, HIF-1α and activation of MMP-9/2 induced by L-OHP and attenuated CIPN in mice. This study suggests that a novel HSP70-TLR-4-p38-TF-HIF-1a axis may play a pivotal role in the pathological process of CIPN. It is also shown that the use of anticoagulant Hirudin can inhibit the above mechanisms and improve CIPN.


Assuntos
Proteínas de Choque Térmico HSP70/genética , Hirudinas/farmacologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Tromboplastina/genética , Animais , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Macrófagos/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Oxaliplatina/efeitos adversos , Oxaliplatina/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
20.
J Pharmacol Sci ; 140(3): 291-294, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31377017

RESUMO

Oxaliplatin induces severe peripheral neuropathy. The effect of donepezil, a drug used for treatment of Alzheimer's disease, on oxaliplatin-induced peripheral neuropathy was investigated using both in vivo and in vitro models. Donepezil effectively attenuated oxaliplatin- and cisplatin-induced inhibition of neurite outgrowth in cultured PC12 cells. In a rat model, repeated oral administration of donepezil (5 times/week for 4 weeks) ameliorated oxaliplatin-induced mechanical allodynia (von Frey test) and sciatic nerve axonal degeneration. Moreover, donepezil did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line. Therefore, donepezil may be useful for managing oxaliplatin-induced peripheral neuropathy.


Assuntos
Donepezila/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxaliplatina/farmacologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Masculino , Camundongos , Células PC12 , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA