Efficacy of Drug Interventions for Chemotherapy-Induced Chronic Peripheral Neurotoxicity: A Network Meta-analysis.
Ontology highlight
ABSTRACT:
SUBMITTER: Fu X
PROVIDER: S-EPMC5462987 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.
| S-EPMC8804126 | biostudies-literature
Project description:In view of advances in early detection and treatment, the 5-year relative survival rate for all cancer patients combined is now approximately 66%. As a result, there are more than 13.7 million cancer survivors in the United States, with this number increasing by 2% annually. For many patients, improvements in survival have been countered by therapy-associated adverse effects that may seriously impair long-term functional status, workplace productivity, and quality of life. Approximately 20% to 40% of cancer patients given neurotoxic chemotherapy develop chemotherapy-induced peripheral neurotoxicity (CIPN), which represents one of the most common and potentially permanent nonhematologic side effects of chemotherapy. Permanent bilateral hearing loss and/or tinnitus can result from several ototoxic therapies, including cisplatin- or carboplatin-based chemotherapy. CIPN and ototoxicity represent important challenges because of the lack of means for effective prevention, mitigation, or a priori identification of high-risk patients, and few studies have applied modern genomic approaches to understand underlying mechanisms/pathways. Translational genomics, including cell-based models, now offer opportunities to make inroads for the first time to develop preventive and interventional strategies for CIPN, ototoxicity, and other treatment-related complications. This commentary provides current perspective on a successful research strategy, with a focus on cisplatin, developed by an experienced, transdisciplinary group of researchers and clinicians, representing pharmacogenomics, statistical genetics, neurology, hearing science, medical oncology, epidemiology, and cancer survivorship. Principles outlined herein are applicable to the construction of research programs in translational genomics with strong clinical relevance and highlight unprecedented opportunities to understand, prevent, and treat long-term treatment-related morbidities.
| S-EPMC4568989 | biostudies-literature
Project description:In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the published literature concerning the evaluation of assessment measures for paediatric chemotherapy-induced peripheral neurotoxicity. We searched PubMed, CINAHL, PsycINFO, and Embase on Nov 7-8, 2018; of 1409 articles, seven met the inclusion criteria. A total of 335 children (excluding ten healthy controls) were enrolled in the seven studies and the sample sizes ranged from 17 to 86 individuals. 276 (82%) of the 335 children were actively undergoing chemotherapy treatment. Most studies did not comprehensively evaluate the psychometric properties of assessment measures for chemotherapy-induced peripheral neurotoxicity. By use of a narrative analysis that combined approaches from the Joanna Briggs Institute (Adelaide, SA, Australia) and the quality of diagnostic accuracy studies assessment method (known as QUADAS), only one study was deemed high quality. We identified two variants of the Total Neuropathy Score, two grading scales, two semi-objective tests, one patient-reported outcome, and several mobility measures. The National Cancer Institute Common Terminology Criteria for Adverse Events and the Balis grading scales showed lower sensitivity and specificity than the items of the Total Neuropathy Score. Although there is insufficient evidence to support the use of most approaches to assess chemotherapy-induced peripheral neurotoxicity in children, two variants of the Total Neuropathy Score, the pediatric-modified Total Neuropathy Score and the Total Neuropathy Score-pediatric vincristine, are promising but require further testing. Other approaches are less sensitive or less feasible. A patient-reported outcome measure for chemotherapy-induced peripheral neurotoxicity in children is needed.
| S-EPMC8152573 | biostudies-literature
Project description:BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is regarded as one of the most common dose-limiting adverse effects of several chemotherapeutic agents, such as platinum derivatives (oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib. CIPN affects more than 60% of patients receiving anticancer therapy and although it is a nonfatal condition, it significantly worsens patients' quality of life. The number of analgesic drugs used to relieve pain symptoms in CIPN is very limited and their efficacy in CIPN is significantly lower than that observed in other neuropathic pain types. Importantly, there are currently no recommended options for effective prevention of CIPN, and strong evidence for the utility and clinical efficacy of some previously tested preventive therapies is still limited.MethodsThe present article is the second one in the two-part series of review articles focused on CIPN. It summarizes the most recent advances in the field of studies on CIPN caused by oxaliplatin, the third-generation platinum-based antitumor drug used to treat colorectal cancer. Pharmacological properties of oxaliplatin, genetic, molecular and clinical features of oxaliplatin-induced neuropathy are discussed.ResultsAvailable therapies, as well as results from clinical trials assessing drug candidates for the prevention of oxaliplatin-induced neuropathy are summarized.ConclusionEmerging novel chemical structures-potential future preventative pharmacotherapies for CIPN caused by oxaliplatin are reported.
| S-EPMC7329798 | biostudies-literature
Project description:Background: Chemotherapy-induced peripheral neuropathy (CIPN) has no cure, but acupuncture may provide relief through its known neuromodulation or neuroendocrine adjustment. This review aimed to assess the efficacy of acupuncture in treating CIPN. Method: A literature review following the PRISMA Statement was performed, searching 7 databases from inception through August 2019. All studies were clinical trials of the effect of acupuncture on CIPN. The methodological quality of these trials was assessed using Cochrane criteria; meta-analysis software (RevMan 5.2) was used to analyze the data. Data Sources: The databases searched were the following: MEDLINE (Ovid), Embase, Cochrane CENTRAL, Scopus, World Health Organization International Clinical Trials Registry Platform, CNKI (China National Knowledge Infrastructure), and Wanfang Med Online. Results: We examined 386 cancer patients from 6 randomized control trials, which had high quality, based on the modified Jadad scale. Meta-analysis showed that acupuncture led to significant improvements in pain scores (-1.21, 95% confidence interval [CI] = -1.61 to -0.82, P < .00001) and nervous system symptoms based on Functional Assessment of Cancer Therapy/Neurotoxicity questionnaire scores (-2.02, 95% CI = -2.21 to -1.84, P < .00001). No significant change was noted in nerve conduction velocity (1.58, 95% CI = -2.67 to 5.83, P = .47). Conclusion: Acupuncture can effectively relieve CIPN pain and functional limitation. The limited number of subjects warrants a larger scale study.
| S-EPMC7242803 | biostudies-literature
Project description:INTRODUCTION:Chemotherapy-induced peripheral neuropathy (CIPN) is one of the prevalent and disabling side effects of cancer treatment. However, management strategies for CIPN currently remain elusive, with treatment restricted to neuropathic pain medications, supportive care, and chemotherapy dosing adjustments. This overview explores evidence on the potential benefits and safety of nonpharmacological interventions in preventing and treating CIPN in cancer patients. METHODS:Seven databases were searched for systematic reviews of randomized controlled trials (RCTs). The methodological quality of the selected reviews was assessed by AMSTAR 2, and the quality of evidence was judged by GRADE. Twenty-eight systematic reviews were considered eligible for this review. RESULTS:It was found that nonpharmacological interventions (acupuncture, exercise, herbal medicine, nutritional supplements) provided potential benefits for patients with CIPN. Furthermore, Chinese herbal medicine, administered orally or externally, significantly prevented and/or relieved the incidence and severity of CIPN in comparison to control groups (no additional treatment, placebo, and conventional western medicine). However, the quality of evidence and strength of recommendations were compromised by the inconsistencies and imprecision of included studies. The main concerns regarding the quality of systematic reviews included the lack of sufficiently rigorous a priori protocols, and the lack of protocol registration adopted in the included studies. CONCLUSIONS:Though looking across reviews, Chinese herbal medicine appear generally effective in CIPN, uncertainty remains about the effects of many other nonpharmacological interventions. The evidence on what works was particularly compromised by reporting and methodological limitations, which requires further investigation to be more certain of their effects.
| S-EPMC7476348 | biostudies-literature
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity to widely used chemotherapeutics. Although the exact molecular mechanism of chemotherapy-induced peripheral neuropathy remains elusive, there is consensus that it is caused by damage to the peripheral nervous system leading to sensory symptoms. Recently developed methodologies have provided evidence of expression of drug transporters in the peripheral nervous system. In this literature review, we explore the role for drug transporters in CIPN. First, we assessed the transport of chemotherapeutics that cause CIPN (taxanes, platins, vincristine, bortezomib, epothilones, and thalidomide). Second, we cross-referenced the transporters implicated in genetic or functional studies with CIPN with their expression in the peripheral nervous system. Several drug transporters are involved in the transport of chemotherapeutics that cause peripheral neuropathy and particularly efflux transporters, such as ABCB1 and ABCC1, are expressed in the peripheral nervous system. Previous literature has linked genetic variants in efflux transporters to higher risk of peripheral neuropathy with the taxanes paclitaxel and docetaxel and the vinca alkaloid vincristine. We propose that this might be due to accumulation of the chemotherapeutics in the peripheral nervous system due to reduced neuronal efflux capacity. Thus, concomitant administration of efflux transporter inhibitors may lead to higher risk of adverse events of drugs that cause CIPN. This might prove valuable in drug development where screening new drugs for neurotoxicity might also require drug transporter consideration. There are ongoing efforts targeting drug transporters in the peripheral nervous system to reduce intraneuronal concentrations of chemotherapeutics that cause CIPN, which might ultimately protect against this dose-limiting adverse event.
| S-EPMC7993259 | biostudies-literature
Project description:Oxaliplatin-induced chronic peripheral neurotoxicity (OXCPN) manifests as a loss of sensation and dysesthesia in the distal extremities, which may impair daily activities and increase in incidence with the amount of oxaliplatin delivered. The variation in the reported incidence and severity of OXCPN may be a consequence of differences in the baseline characteristics of patients.This was a prospective study (ClinicalTrials.gov, NCT00977717) in which OXCPN was recorded for all consecutive colon cancer patients treated at Samsung Medical Center (Seoul, Korea) with oxaliplatin-based combination chemotherapy. The primary endpoint was the incidence of severe OXCPN (grade 2 lasting for >7 days, or grade 3). The association of severe OXCPN and pretreatment parameters was evaluated using a multivariate regression model.Between Jan 2008 and Feb 2010, 100 patients treated with adjuvant folinic acid/fluorouracil plus oxaliplatin (FOLFOX) and 266 patients treated with capecitabine plus oxaliplatin (XELOX) or FOLFOX for advanced disease were registered into our study. The median cumulative dose of oxaliplatin was 796 mg/m(2) (range, 85 to 1,583 mg/m(2)). Severe OXCPN was observed in 126 (34%) patients. Overall, 43 patients discontinued chemotherapy due to toxicity: 23 without severe OXCPN and 20 with severe OXCPN. In univariate analysis, severe OXCPN was frequently observed in patients with age ?55 years (p<0.01), stage II or III (p<0.01), adjuvant setting (p=0.01), FOLFOX (p<0.01), performance status of 0 (p=0.02), and those with no prior chemotherapy (p<0.01). In a multivariate regression model, the number of chemotherapy cycles and the cumulative oxaliplatin dose were not associated with the development of severe OXCPN.We failed to find a significant association between patient characteristics at baseline and the development of severe OXCPN after oxaliplatin-based combination chemotherapy. Pharmacogenomic profiling using genome-wide association study in these patients is underway.
| S-EPMC3021736 | biostudies-literature
Project description:PurposeThe Patient Neurotoxicity Questionnaire (PNQ) represents a diagnostic tool concerning patients with chemotherapy-induced peripheral neuropathy (CIPN). The application of such a tool in the Greek clinical praxis requires validation.MethodsValidation consists of three stages - translation, reverse translation, and patient application. Hundred oncologic patients were assessed by comparing the PNQ to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) at the chemotherapy onset and second, fourth, and sixth sessions. The diagnostic tool's specific requirements (compliance, validity, concordance, sensitivity, specificity, reliability) were statistically evaluated.ResultsDifferences between translated texts and between the reverse translation and the original were considered negligible. At the second, fourth, and sixth session compliance was 98%, 95%, and 93% while Cronbach's α was 0,57 0,69, and 0,81, respectively. Cohen's weighted κ was 0,67 and 0,58, Spearman's ρ was 0,7 and 0,98, while the area under the curve (AUC) of the receiver operating characteristic (ROC) was 1 and 0,9 for the sensory and the motor part, respectively. The variance's linear regression analysis confirmed CIPN worsening over time (P<0.0001).DiscussionThe Greek version remains close to the original English version. Compliance rates reflect easy PNQ applications. Cohen's κ values highlight the physicians' tension to underestimate the patients' condition. Spearman's ρ, Cronbach's α, and AUC values reflect good validity, reliability, and specificity of the PNQ respectively. Finally, the linear analysis confirmed the PNQ sensitivity over time.ConclusionsThe PNQ validation in Greek adds a crucial tool to the physicians' armamentarium. It can now delineate the necessary information to modify the chemotherapy and analgesic treatment regimens at both preventive and acute levels.
| S-EPMC8025796 | biostudies-literature
Project description: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.
| S-EPMC7220547 | biostudies-literature