Management Of Chemotherapy-induced Peripheral Neuropathy Research Articles

Comparative Efficacy of Tapentadol versus Tapentadol Plus Duloxetine in Patients with Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Randomized Non-Inferiority Clinical Trial.

Simple SummaryChemotherapy-induced peripheral neuropathy (CIPN) is a common complication due to treatment with anti-cancer agents. Our aim was therefore to assess the non-inferiority of the analgesic effect and safety of tapentadol alone compared to duloxetine plus tapentadol administered to patients with chemotherapy-induced peripheral neuropathy. The use of tapentadol is a safe and effective analgesic therapy in patients with CIPN. Positive effects of tapentadol were noted on the patients’ quality-of-life assessments.Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication due to treatment with many commonly used anti-cancer agents. CIPN is a mainly sensory neuropathy that can be characterized by the appearance of motor and autonomic alterations. Clinicians may offer duloxetine (DLX) for patients with cancer experiencing CIPN. Our aim was to assess the non-inferiority of the analgesic effect and safety of tapentadol (TP) alone compared to duloxetine plus tapentadol administered to patients with CIPN. Methods: A total of 114 patients were enrolled in the study and randomized to receive tapentadol in a dosage of 50 to 500 mg/day (n = 56) or tapentadol plus duloxetine in a dosage of 60 to 120 mg/day (n = 58) for a period of 4 weeks. We evaluated the analgesia efficacy, defined as a decrease in pain on the NRS between the first administration and 28 days later. Secondary endpoints included analgesia efficacy at 28 and 42 days, defined by a decrease in DN4 and LEPs, decrease in quality of life, and the incidence of any serious or non-serious adverse events after the first administration. Results: In this randomized, double-blind trial comparing TP and TP plus DLX for CIPN management, TP was feasible and non-inferior to the association with DLX as far as the reduction of pain after chemotherapy at 28 days is concerned. Scores on other rating scales evaluating the quality of life, anxiety and depression, and the characteristics of pain revealed similar improvements associated with tapentadol versus duloxetine at these time points. Conclusion: The use of TP is a safe and effective analgesic therapy in patients with CIPN. Positive effects of TP were noted on the patients’ quality-of-life assessments.

Exploring Patients' Understanding of Chemotherapy-Induced Peripheral Neuropathy.

Little quantitative evidence exists surrounding patients' level of understanding of chemotherapy-induced peripheral neuropathy (CIPN) symptoms (numbness, tingling, pain in the hands/feet) and consequences (e.g., negatively affect physical functioning or chemotherapy dosing) at the beginning of chemotherapy. The purpose of this cross-sectional, secondary analysis was to describe CIPN knowledge and education patterns among adults early in a course of neurotoxic chemotherapy for the treatment of cancer (< three infusions). Following consent, participants completed an electronic questionnaire about their perceptions of CIPN symptoms, incidence, and education. Participants (N = 92) were mainly female (76%), white (91%), and diagnosed with breast (46%) or gastrointestinal (40%) cancers. Most participants without CIPN (n = 48) did not expect to develop CIPN (45%) or were unaware of CIPN as a side-effect (30%). Furthermore, 71% of participants without CIPN (n = 31) estimated CIPN to occur in ≤ 30% of patients receiving neurotoxic chemotherapy. Overall, participants learned about CIPN from their doctor or nurse prior to beginning chemotherapy (90%). Clinicians delivered education about CIPN symptoms (75%), but less frequently delivered education about CIPN management (14%), or the impact of CIPN on the ability to continue chemotherapy (16%) or physical functioning (24%). Finally, participants reported that a discussion with their doctor/nurse would be the best way to learn about CIPN (92%). Results revealed that participants without CIPN were largely unaware of the adverse consequences or incidence of CIPN during treatment. Further research is needed to investigate optimal methods to promote patient-clinician communication about CIPN during chemotherapy to enhance patients' retention of CIPN information and activation in their care.

Evaluating the safety, feasibility, and efficacy of non-invasive neuromodulation techniques in chemotherapy-induced peripheral neuropathy: A systematic review

This systematic review was conducted to evaluate the best available evidence regarding the use of non-invasive neuromodulation techniques for managing chemotherapy-induced peripheral neuropathy (CIPN). A systematic literature search of the following databases from their inception to October 17, 2021 was performed and was updated on March 2, 2022: AMED via Ovid, CINAHL via the EBSCO Host, Cochrane Library, Embase, PEDro, PubMed, and Web of Science. Randomized controlled trials (RCTs) and quasi-experimental studies examining the safety, feasibility, and efficacy of non-invasive neuromodulation techniques for managing established CIPN were identified. Narrative synthesis was used to analyze data collected from the included studies. Nine RCTs and nine quasi-experimental studies were included. A variety of non-invasive peripheral and central neuromodulation techniques were investigated in those studies, including scrambler therapy, electrical stimulations, photobiomodulation, magnetic field therapy, therapeutic ultrasound, neurofeedback, and repetitive transcranial magnetic stimulation. Non-invasive neuromodulation techniques for the management of established CIPN are generally safe and feasible. The efficacy of peripheral neuromodulation techniques such as scrambler therapy and transcutaneous electrical nerve stimulation was mostly unsatisfactory, while central neuromodulation techniques such as neurofeedback and repetitive transcranial magnetic stimulation were promising. The use of non-invasive neuromodulation techniques for managing CIPN is still in its infancy. Non-invasive central neuromodulation techniques have significant potential for relieving chronic pain and neuropathic symptoms related to CIPN, meriting further exploration.

Risk Factors for Nab-Paclitaxel and Gemcitabine-Induced Peripheral Neuropathy in Patients with Pancreatic Cancer

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent adverse events observed with taxane use, whose disability often required modification or treatment discontinuation. The aim of this study was to assess the value of several variables as risk factors for CIPN development. Material and Methods: Eligible patients with metastatic pancreatic cancer receiving chemotherapy with nab-paclitaxel and gemcitabine were assessed in a multicenter study. Peripheral neuropathy was categorized using the National Cancer Institute Common Toxicity Criteria scale, version 4.02, and a physical/neurological examination. Univariate and multivariate regression analyses were used to identify blood-based and clinical factors associated with CIPN. Results: Data were available from 153 patients from five Italian centers. Key risk factors of CIPN in univariate regression models included age, number of chemotherapy cycles, statin assumption, and concomitant comorbidities. However, in the multivariate analysis, only for age (OR 1.0, p < 0.01, 95% CI: 1.01–1.11) and the number of cycles (OR 1.22, p < 0.01, 95% CI: 1.09–1.36), the correlation with CIPN development has been confirmed. Conclusion: Our study confirms age and the number of chemotherapy cycles as CIPN risk factors. The identification and validation of different risk factors could be advantageous to prevent or optimize management of CIPN which outstandingly affect the patient’s quality of life.

Development and consensus process for a clinical pathway for the assessment and management of chemotherapy-induced peripheral neuropathy

BackgroundCancer patients treated with neurotoxic chemotherapy are at risk of developing neurological symptoms that can impact functional capacity and quality of life. However, there are no standardised pathways to assess and manage chemotherapy-induced peripheral neurotoxicity (CIPN). This study aimed to determine consensus on statements regarding a CIPN assessment and management clinical pathway.MethodsA CIPN clinical pathway (CIPN-path) was developed and reviewed by an expert multi-disciplinary panel and consumers. Agreement with 18 statements regarding four content themes (pretreatment review, screening and assessment, management and referral, and CIPN-path feasibility) were assessed by 70 Australian respondents (68 health professionals, 2 consumers), using a 2-stage Delphi survey process to reach consensus. Respondents rated statements using a 5-point Likert scale to determine the level of agreement, with consensus defined as ≥ 80% of respondents agreeing with each statement.ResultsThe consensus was reached for 14 of 18 items after stage 1 and all items after stage 2. Feedback was obtained for all items to refine the CIPN-path. There was an agreement on important characteristics of the CIPN-path, including pretreatment screening, regular patient-reported assessment, and a stepped-care approach to investigating and managing symptom burden. There was a lack of agreement on who should oversee CIPN assessment, which may differ according to the structure and resources of each site.ConclusionsThere was an overall agreement concerning the CIPN-path to assess and manage CIPN, which may be adapted accordingly to the resources of each clinic. The CIPN-path may assist teams across different health services in identifying CIPN symptoms, aiding decision-making, and reducing morbidity from CIPN.

Analgesic and preventive effects of donepezil in animal models of chemotherapy-induced peripheral neuropathy: Involvement of spinal muscarinic acetylcholine M2 receptors

BackgroundDonepezil, a cholinesterase inhibitor approved in Alzheimer’s disease, has demonstrated analgesic and preventive effects in animal models of oxaliplatin-induced neuropathy. To improve the clinical interest of donepezil for the management and prevention of chemotherapy-induced peripheral neuropathy (CIPN), a broader validation is required in different animal models of CIPN. Methods: using rat models of CIPN (bortezomib, paclitaxel, and vincristine), the analgesic and preventive efficacies of donepezil were evaluated on tactile, cold and heat hypersensitivities. The involvement of muscarinic M2 acetylcholine receptors (m2AChRs) in analgesic effects was investigated at the spinal level. The absence of interference of donepezil with the cytotoxic effect of chemotherapy has been controlled in cancer cell lines. Results: the analgesic efficacy of donepezil was demonstrated for all CIPN models, mainly on tactile hypersensitivity (maximal efficacy at 60 min, p < 0.05 vs. vehicle group). This effect was suppressed by an intrathecal injection of methoctramine (m2AChR antagonist). Regarding preventive effects, donepezil limited tactile hypersensitivity induced by paclitaxel, but not for other CIPN models. Donepezil did not modify the viability of cancer cells or the efficacy of anticancer drugs. Conclusions: donepezil had a broad analgesic effect on animal models of CIPN and this effect involved spinal m2AChRs. This work validates the repositioning of donepezil in the management of CIPN.

Exploring Clinicians' Perspectives of Barriers to Chemotherapy-Induced Peripheral Neuropathy Assessment and Management in Oncology Practice: A Qualitative Analysis of Semi-structured Interviews.

Quantitative reports suggest that the assessment and management of chemotherapy-induced peripheral neuropathy (CIPN) in practice is suboptimal. The purpose of this qualitative analysis was to explore clinician-related perspectives of CIPN assessment, management, and the use of a CIPN decision support tool. Clinicians from the breast oncology, gastrointestinal oncology, or multiple myeloma disease centers at Dana-Farber Cancer Institute who interacted with a CIPN clinician decision support algorithm were eligible to participate in the semi-structured interviews. The interview guide included questions about CIPN assessment, management, and clinician-decision support tool use. All interviews were audio-recorded, transcribed, and analyzed using inductive content analysis. Of the 39 eligible clinicians, 15 agreed to be interviewed. Interviewed clinicians were mainly physicians (73.3) and White, non-Hispanic (93.3%). Main themes from the interviews included (1) CIPN management practice patterns (eg, endorsement of non-recommended management strategies or lack of standardization for chemotherapy dose reduction) and barriers (eg, insurance prior authorizations required for duloxetine prescription), (2) CIPN assessment practice patterns (eg, use of subjective instead of objective CIPN assessment approaches) and barriers (eg, difficult to interpret patients' CIPN report between visits), and (3) utilization of the clinician decision support tool (eg, all assessment tasks lead to same management options). There are several barriers to clinicians' use of evidence-based CIPN assessment and management strategies. Future work should be focused on addressing barriers to duloxetine prescription, developing evidence-based CIPN assessment and management strategies, improving symptom monitoring, and facilitating referrals to existing supportive care services.

Pharmacological and Nonpharmacological Management of Chemotherapy-Induced Peripheral Neuropathy: A Scoping Review of Randomized Controlled Trials.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment with no effective preventative strategy or definitive treatment. Purpose: To synthesize empiric literature from randomized controlled trials (RCTs) of pharmacological and nonpharmacological management of CIPN. Data Sources: Articles published between January 1, 2010, and February 28, 2021, were identified using keywords searching Medline, PubMed, CINAHL, Web of Science, Cochrane Library, and Embase. Study Selection: RCTs that recruited individuals who were post-chemotherapy and experienced persistent CIPN symptoms. Data Extraction and Synthesis: Three independent reviewers screened a total of 2023 abstracts. After screening, full-text review, and quality appraisal, 22 articles were included in this review. Data related to study design, participant characteristics, interventions, controls, outcome measures, and relevant findings were extracted from full texts. Descriptive quantitative summaries were calculated and narrative analysis was performed. Results: Of the 22 studies, 4 investigated pharmacologic treatments, 2 compared acupuncture to pharmacologic treatments, and 16 studies examined nonpharmacologic treatments. Pharmacologic studies reported mixed results with evidence of participant response varying by history of chemotherapeutic agent. Acupuncture, exercise/physical therapy, and neurofeedback appear to be effective treatments for CIPN. Evidence regarding biophysical agents and cognitive-behavioral therapy is equivocal. Scrambler therapy is not supported. Limitations: Studies included in this review share several limitations, including widely variable outcome measures, small and demographically homogenous samples, and nonstandardized treatment protocols. Conclusion: This scoping review summarized the current body of high-quality RCTs investigating treatment for CIPN. The majority of studies in this review reports benefits of pharmacologic and nonpharmacologic interventions, although management may require a multipronged approach and should be tailored to the individual. Clinical implications are proposed and suggestions made for future research include implementation of standardized intervention protocols, use of outcome measures representative of the spectrum of CIPN symptoms, and stratification by the chemotherapeutic agent.

Clinician and patient experiences when providing and receiving information and support for managing chemotherapy-induced peripheral neuropathy: A qualitative multiple methods study.

ObjectiveTo improve patient experience of chemotherapy‐induced peripheral neuropathy (CIPN), it is crucial to identify how patients develop their understanding and perception of CIPN. A wider understanding of the experiences of clinicians who provide CIPN information and support is also needed. This study explored clinician and patient experience of the provision of care, information and support for CIPN.MethodsData were collected between July and November 2019 using multiple qualitative methods. Non‐participant observations were undertaken in colorectal and breast cancer clinics and at clinician stations, including the observation of chemotherapy consultations between patients and clinicians. Semi‐structured interviews with people with cancer and clinicians were also conducted. Data were analysed using inductive reflexive thematic analysis.ResultsThree major themes emerged: (1) CIPN is a hidden chemotherapy side effect, (2) assessment and management of CIPN is disconnected and (3) patients and clinicians expect openness in CIPN symptom reporting, information provision and management.ConclusionFindings show the need to address the lack of patients' overall familiarity with CIPN. Echoing earlier studies, our findings suggest that knowledge and understanding about CIPN among clinicians are limited or lacking. These insights from patient and clinicians' CIPN experiences can inform future interventions that may address the genuine needs of patients and enhance CIPN support.

The effect of salt-water bath in the management of treatment-related peripheral neuropathy in cancer patients receiving taxane and platinum-based treatment

ObjectivesIn a clinical setting, patients have been observed to complain of discomfort and to discontinue treatment because of chemotherapy-induced peripheral neuropathy. This experimental study was conducted to determine the effect of a salt-water bath in the management of chemotherapy-induced peripheral neuropathy. MethodOne hundred and three patients who received taxane and platinum-based chemotherapy due to cancer and developed peripheral neuropathy associated with the treatment between December 2018 and June 2020 were included in the study. The patients were assigned to the control and experimental groups (1-warm salt-water and 2-cold salt-water) following the randomization checklist. While control groups did not receive any interventions, the patients in the salt-water group were asked to apply warm (41 °C) or cold-water (23–26 °C) baths to their hands/feet for 30 min every other day for 14 days. The data were collected at the beginning of the study and at the end of its first and second weeks using the Patient Information Form and National Cancer Institute (NCI)-CTCAE v5.0 toxicity criteria as well as the EORTC QLQ-C30 and EORTC QLQ-CIPN20 quality of life scales. ResultsThe patients had a mean age of 55.6 ± 10.3, and most of them were treated following a breast cancer diagnosis. At the beginning of the study, Grade 3 peripheral neuropathy severity and quality of life scores of the cold/warm salt-water and control groups were similar. Due to repeated follow-ups, it was determined that the peripheral neuropathy severity decreased and the quality of life scores increased statistically significantly in the patients in the cold salt-water bath group compared to the control group. ConclusionThis study's results suggest that a cold salt-water bath can be an effective approach in managing the development of peripheral neuropathy due to taxane and platinum-based treatment.

Cold Application and Exercise on Development of Peripheral Neuropathy during Taxane Chemotherapy in Breast Cancer Patients: A Randomized Controlled Trial

Objective:Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. There is no proven pharmacological application to prevent CIPN. This study was conducted to compare the effects of cold application and exercise on peripheral neuropathy development in patients with breast cancer who received taxane.Methods:This was a multicenter clinical trial. The study was conducted as a randomized controlled trial on breast cancer patients who had chemotherapy-induced peripheral neuropathy complaints between July 2017 and January 2018 in an outpatient chemotherapy unit of training-research and a university hospital. A standardized, home-based, 12-week exercise program involved progressive strengthening, stretching, and balance exercises. Cold packs were applied for the duration of all 12 taxane infusions and then continued at home. The standard care protocol (information about side effects) of the clinic was used for patients in the control group. Data were collected via Patient Identification Form and CIPN Assessment Tool. Demographic data were evaluated by number and percentage ratios, and the study groups' mean scores were compared by Kruskal–Wallis and Wilcoxon analyses. The data were collected at two time points including baseline (T1) and week 12 (T2).Results:The study was completed with a total of 90 patients, so that each of the study groups, exercise, cold application, and control groups, included 30 patients. The mean of pre- and posttest results in the cold applied group revealed an increase in hand numbness, weakness, and distress (P < 0.05). However, no significant difference existed between the means of the pre- and the posttests in the exercise group (P = 0.79–0.1). The mean scores of all the symptoms in the control group except the loss of balance increased significantly (P < 0.05). Exercise reduced CIPN symptoms of numbness in hands (P = 0.009) and in the feet (P = 0.005) significantly compared to the cold application and control.Conclusions:It was found that exercise was more effective than cold application in the management of CIPN.

Antioxidants Improve Oxaliplatin-Induced Peripheral Neuropathy in Tumor-Bearing Mice Model: Role of Spinal Cord Oxidative Stress and Inflammation

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, difficult-to-treat, and dose-limiting side effect associated with Oxaliplatin (OXA) treatment. In this study, we evaluated the effect of three antioxidants - namely N-acetylcysteine, α-lipoic acid and vitamin E – upon nociceptive parameters and antitumor efficacy of OXA in a tumor-bearing Swiss mice model. Oral treatment with antioxidants inhibited both mechanical and cold allodynia when concomitantly administrated with OXA (preventive protocol), as well as in animals with previously established CIPN (therapeutic protocol). OXA increased Reactive Oxygen Species (ROS) production and lipoperoxidation, and augmented the content of pro-inflammatory cytokines (IL-1β and TNF-α) and expression of the astrocytic marker Gfap mRNA in the spinal cord. Antioxidants decreased ROS production and lipoperoxidation, and abolished neuroinflammation in OXA-treated animals. Toll-like receptor 4 (Tlr4) and inflammasome enzyme caspase-1/11 knockout mice treated with OXA showed reduced levels of pro-inflammatory cytokines (but not oxidative stress) in the spinal cord, which were associated with resistance to OXA-induced mechanical allodynia. Lastly, antioxidants affected neither antitumor activity nor hematological toxicity of OXA in vivo. The herein presented results are provocative for further evaluation of antioxidants in clinical management of chemotherapy-induced peripheral neuropathy. PerspectiveThis study reports preventive and therapeutic efficacy of orally administrated antioxidants (N-acetylcysteine, α-lipoic-acid and Vitamin-E) in alleviating oxaliplatin-induced peripheral neuropathy in tumor-bearing mice. Antioxidants’ anti-nociceptive effects are associated with inhibition of ROS-dependent neuroinflammation, and occur at no detriment of OXA antitumor activity, therefore indicating a translational potential of these compounds.

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing.

Prevention, diagnosis and management of chemotherapy-induced peripheral neuropathy: a cross-sectional study of French oncologists' professional practices.

Chemotherapy-induced peripheral neuropathy (CIPN) is challenging for oncologists. Many publications mention the high incidence of CIPN and the lack of effective preventive/management strategies and robust diagnostic tools. This cross-sectional study was aimed at assessing the practice of French oncologists for CIPN prevention, diagnosis and management. This web-based survey was sent to French oncologists by the regional cancer networks. Incidence and impact of CIPN were assessed using visual analogue scales (VAS) and diagnostic strategies were recorded. Also recorded were the drugs used to prevent or manage CIPN and their perceived efficacy and safety (VAS). Among the 210 oncologists included, the perceived incidence of CIPN was about 36.2 ± 22.1% of patients. About 99.5% of oncologists declared that they assess CIPN during medical follow-up. The use of drugs to prevent CIPN was reported by 9.6% of oncologists (group B vitamins (35.0%) and calcium and magnesium infusion (25.0%)). In the case of CIPN, the therapeutic adjustment of neurotoxic anticancer drugs is performed by 99.0% of oncologists (chemotherapy change (49.8%), dose reduction (30.9%) or interruption (19.3%)). The pharmacological management of CIPN was declared by 72.9% of oncologists. The main drugs used are pregabalin (75.8%), amitriptyline (32.7%) and gabapentin (25.5%). Duloxetine (ASCO recommendation) is used by only 11.8% of oncologists. Oncologists were clearly aware of CIPN risks, but its incidence tended to be underestimated and the ASCO recommendations for the management of CIPN were not followed. The prevention, diagnosis and management of CIPN remain problematic in clinical practice in France. ClinicalTrials.gov : NCT03854864.

An overview of ongoing clinical trials assessing pharmacological therapeutic strategies to manage chemotherapy-induced peripheral neuropathy, based on preclinical studies in rodent models.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect induced by a variety of chemotherapeutic agents. Symptoms are mainly sensory: pain, tingling, numbness, and temperature sensitivity. They may require the tapering of chemotherapy regimens or even their cessation; thus, the prevention/treatment of CIPN is critical to increase effectiveness of cancer treatment. However, CIPN management is mainly based on conventional neuropathic pain treatments, with poor clinical efficacy. Therefore, significant effort is made to identify new pharmacological targets to prevent/treat CIPN. Animal modeling is a key component in predicting human response to drugs and in understanding the pathophysiological mechanisms underlying CIPN. In fact, studies performed in rodents highlighted several pharmacological targets to treat/prevent CIPN. This review provides updated information about ongoing clinical trials testing drugs for the management of CIPN and presents some of their proof-of-concept studies conducted in rodent models. The presented drugs target oxidative stress, renin-angiotensin system, glutamatergic neurotransmission, sphingolipid metabolism, neuronal uptake transporters, nicotinamide adenine dinucleotide metabolism, endocannabinoid system, transient receptor potential channels, and serotoninergic receptors. As some clinical trials focus on the effect of the drugs on pain, others evaluate their efficacy by assessing general neuropathy. Moreover, based on studies conducted in rodent models, it remains unclear if some of the tested drugs act in an antinociceptive fashion or have neuroprotective properties. Thus, further investigations are needed to understand their mechanism of action, as well as a global standardization of the methods used to assess efficacy of new therapeutic strategies in the treatment of CIPN.

Lagged Relationships Among Chemotherapy-Induced Peripheral Neuropathy, Sleep Quality, and Physical Activity During and After Chemotherapy.

Chemotherapy-induced peripheral neuropathy (CIPN) is well-documented and can become chronic for up to a third of patients. CIPN management is hampered by limited pharmacological options. Thus, identifying modifiable behaviors that influence CIPN may help inform future interventions. The purpose of the current study was to examine bidirectional relationships between sleep quality, physical activity, and CIPN during and after chemotherapy. Participants were 138 women with gynecologic cancer (M age = 61, 94% white, 96% non-Hispanic), collected as part of an ongoing study. Assessments occurred at postcycle 1, postcycle 6, and 6- and 12-month postchemotherapy. CIPN (EORTC-CIPN20), sleep quality (PSQI), and physical activity (IPAQ) were assessed via self-report. Objective physical activity was assessed via wrist actigraphy. Latent change score models were used to examine lagged relationships between CIPN, sleep quality, and physical activity pairs. Over the study period, sleep quality was found to contribute to CIPN (p = .001), but not the reverse (p > .05). Bidirectional relationships were observed between CIPN and both objective and subjective walking (ps ≤ .001). Illustrations of these relationships showed that patients with less CIPN early in treatment demonstrate more substantial increases in walking over time, while those with higher CIPN demonstrate more consistent levels of walking during and after treatment. These findings suggest that worse sleep quality and lower walking levels may contribute to the course and maintenance of CIPN. Future investigation should evaluate the impact of early interventions aimed at improving sleep quality and encouraging physical activity in patients treated with chemotherapy.

Physiotherapy management of chemotherapy-induced peripheral neuropathy in Pretoria, South Africa.

BackgroundThe increase in newly diagnosed patients with cancer in South Africa and globally, may contribute to the increase in patients living with chemotherapy-induced peripheral neuropathy (CIPN). Chemotherapy-induced peripheral neuropathy negatively impacts on quality of life (QoL) during and post chemotherapy treatment. Physiotherapy management of CIPN helps patients to manage symptoms and improves function in activity- and participation-levels to ultimately improve QoL. However, little evidence exists regarding the type or combination of physiotherapy management strategies in South Africa.ObjectivesThe purpose of our study was to determine how the symptoms of CIPN were managed by physiotherapists in Pretoria, South Africa.MethodA quantitative, descriptive study design was used. Electronic questionnaires were distributed to physiotherapists who worked with cancer patients and who treated patients with CIPN.ResultsPhysiotherapists used massage, proprioceptive neuromuscular facilitation, sensory integration, activities of daily living training, postural drainage, lifestyle modifications; Bobath-, breathing-, stability-, stretching-, strengthening- and endurance-exercises; electrical stimulation, thermal modalities, transcutaneous electrical nerve stimulation, soft tissue mobilisation; muscle energy-, positional- and Mulligan-techniques in the management of CIPN.ConclusionCardiopulmonary therapy, therapeutic exercises, manual therapy and neuro-developmental techniques were used by physiotherapists in the management of CIPN. Almost half of the participants did not use electrotherapy techniques. Physiotherapy management strategies that are used in Pretoria are similar to published research.Clinical implicationsPhysiotherapists in Pretoria are managing CIPN according to international practices. However, studies to determine the effectiveness of the management strategies in a South African context should be conducted. Alternative management strategies, based on the pathophysiology of CIPN, should be explored.Keywordsphysiotherapy; chemotherapy-induced peripheral neuropathy; intervention; management; cancer.

Duloxetine hydrochloride loaded film forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats

ObjectiveIn attempt to conquer the major concerns of oral duloxetine hydrochloride (like low bioavailability, intolerable side-effects and no regeneration of demyelinated nerve fibres) for the management of chemotherapy-induced peripheral neuropathy (CIPN), an alternative delivery of duloxetine hydrochloride was aimed for in-vivo optimization. MethodsA film forming dermal gel consisting of duloxetine hydrochloride was formulated and enriched with methylcobalamin and geranium oil. The formulated gel successfully qualified the various pharmaceutical characteristics of gel. Administration of paclitaxel (8 mg/kg/i.p. in four divided doses) for 4 alternate days induced the symptoms of peripheral neuropathy in rats. On 14th day, the responses to noxious stimulus (mechanical hyperalgesia, cold allodynia, and heat hyperalgesia) were increased and reached to its maximum. Thereafter, drug treatment with formulated dermal gel and oral duloxetine hydrochloride (30 mg/kg, once daily) was initiated for 2 weeks in different group of animals. On the 28th day animals were sacrificed to isolate sciatic nerve, to assess biochemical changes (TBARS, reduced GSH, total protein, TNF-α, IL-6) and for histopathological examinations of nerve sections using Hematoxylin-Eosin and Toludine blue staining methods. ResultsApplication of formulated dermal gel to paclitaxel-treated rats significantly improved paw-withdrawal latency responses during noxious stimulus testing, reduced the levels of TBARS, TNF-α, IL-6 and elevated the levels of reduced GSH as compared to paclitaxel treated rats. Histographs also indicated marked regeneration of the damaged nerve fibers. Topical delivery of duloxetine hydrochloride produced similar results in disparity to oral route. However, no significant disparity in responses was obtained with twice application of formulated dermal gel when compared to once daily application. ConclusionTremendous recovery from nociception, oxidation and inflammation in addition to nerve degeneration was achieved through dermal application of duloxetine hydrochloride in peripheral neuropathy.

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update.

To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. An Expert Panel conducted targeted systematic literature reviews to identify new studies. The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.

Photobiomodulation Therapy for the Management of Chemotherapy-Induced Peripheral Neuropathy: An Overview.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy (CT), affecting 68% of patients. Current treatment strategies are based on pharmacological symptom management, but have limited results. Photobiomodulation therapy (PBMT) is a new and emerging therapeutic tool in the supportive care of cancer patients. In this overview, we explore the usability of PBMT for management of CIPN. Objective: To provide a comprehensive overview of management of CIPN with PBMT. Methods: Specific terms, including "Photobiomodulation Therapy," "Drug Therapy," and "Peripheral Nervous System Diseases," were identified for the literature research in PubMed. Results: Three articles were considered eligible for this review. Primary outcome measures were highly variable across the included studies. Conclusions: PBMT might be an effective treatment strategy to manage CIPN, with very encouraging reports from renowned teams, but evidence is limited. More methodologically uniform research (mainly regarding the parameters of PBMT) is needed to support the use of PBMT for this indication.