Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3)

BACKGROUND: The antiepileptic agent, gabapentin, has been demonstrated to relieve symptoms of peripheral neuropathy due to various etiologies. On the basis of these data, a multicenter, double-blind, placebo-controlled, crossover, randomized trial was conducted to evaluate the effect of gabapentin on symptoms of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Patients with symptomatic CIPN who complained of 'average' daily pain scores of either 1) >/=4 on a 0-10 numerical rating scale (NRS); or 2) >/=1 on the 0-3 Eastern Cooperative Oncology Group neuropathy scale (ENS) were eligible (higher numbers indicate greater severity of symptoms in both scales). Patients were randomized to receive gabapentin (target dose, 2700 mg) or placebo for 6 weeks. Crossover occurred after a 2-week washout period. CIPN-related symptoms were evaluated weekly by questionnaires. Statistical methods followed established methods for crossover designs, including Student t tests to compare average intrapatient differences between treatments and linear models to adjust for potential concomitant covariates. RESULTS: There were 115 patients who were randomly assigned to the treatment or control arm. Both groups were well matched by symptoms at study entry. Changes in symptom severity were statistically similar between the 2 groups during the study. Adverse events were mild and similar in both groups. CONCLUSIONS: This trial failed to demonstrate any benefit to using gabapentin to treat symptoms caused by CIPN.     

Predictors of duloxetine response in patients with oxaliplatin‐induced painful chemotherapy‐induced peripheral neuropathy (CIPN): a secondary analysis of randomised controlled trial – CALGB/alliance 170601

Duloxetine is an effective treatment for oxaliplatin‐induced painful chemotherapy‐induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. The objective of this secondary and exploratory analysis was to identify predictors of duloxetine response in patients with painful oxaliplatin‐induced CIPN. Patients (N = 106) with oxaliplatin‐induced painful CIPN were randomised to receive duloxetine or placebo. Eligible patients had chronic CIPN pain and an average neuropathic pain score ≥4/10. Duloxetine/placebo dose was 30 mg/day for 7 days, then 60 mg/day for 4 weeks. The Brief Pain Inventory‐Short Form and the EORTC QLQ‐C30 were used to assess pain and quality of life, respectively. Univariate and multiple logistic regression analyses were performed to identify demographic, physiologic and psychological predictors of duloxetine response. Higher baseline emotional functioning predicted duloxetine response (≥30% reduction in pain; OR 4.036; 95% CI 0.999–16.308; p = 0.050). Based on the results from a multiple logistic regression using patient data from both the duloxetine and placebo treatment arms, duloxetine‐treated patients with high emotional functioning are more likely to experience pain reduction (p = 0.026). In patients with painful, oxaliplatin‐induced CIPN, emotional functioning may also predict duloxetine response. ClinicalTrials.gov, Identifier NCT00489411     

Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years.

Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search.

Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect.     

Anemia Is a Novel Predictive Factor for the Onset of Severe Chemotherapy-Induced Peripheral Neuropathy in Lymphoma Patients Receiving Rituximab Plus Cyclophosphamide,Doxorubicin, Vincristine,and Prednisolone Therapy

Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in lymphoma patients receiving R-CHOP, a drug combination therapy. Although severe CIPN may lead to reduction and/or discontinuation of the medication, predictive factors of CIPN have not been investigated sufficiently to date. We performed a retrospective exploratory research to determine associations between prevalence of severe CIPN and sociodemographic data, health characteristics, and medical conditions such as anemia at initial diagnosis. Forty patients (indolent lymphoma, n=9; diffuse large B-cell lymphoma; n=31) received R-CHOP therapy from September 2009 to July 2014. The median age of patients was 58 years (range=27–76 years). Statistical analyses were applied to the patients, who were divided into two groups: mild CIPN (no symptoms or grade 1 according to the CTCAE version 3.0 program) and severe CIPN patients (grade 2 or higher). Forward stepwise logistic regression analyses were performed using the following variables: sex, BMI, BSA, hyperglycemia, malnutrition, and anemia. Severe CIPN occurred in seven patients (17.5%). Gender and anemia remained following the stepwise procedure, and anemia predicted severe CIPN significantly (OR=19.45, 95% confidence interval=1.52–171.12). Our study suggests that anemia at initial diagnosis could be a predictive factor of R-CHOP-induced CIPN.     

PainVision系统量化评估癌痛及化疗神经毒性的应用分析

背景与目的：癌症相关性疼痛是晚期肿瘤患者的重要临床症状,而化疗常导致周围神经病变,引发疼痛,严重影响患者的生活质量。目前癌痛的评估大都通过患者主观量表来实现,缺乏客观评价手段。本研究借助PainVision系统(PV法)从神经电生理角度定量地进行癌痛评估,检测分析化疗导致的神经病变程度。方法：癌痛患者通过数字疼痛强度量表(numerical rating scale,NRS)主观量表和PV法同时进行疼痛评估,将PV法所得检测值与NRS评分进行相关性分析;对化疗患者进行电流知觉阈值(current perception threshold,CPT)检测,了解化疗对患者CPT水平的影响,尝试PV法进行化疗神经毒性的检测。结果：癌痛患者所测得疼痛比(PainRatio)和患者NRS评分线性相关(Pearson系数为0.849,P＜0.001);伴有神经毒性临床症状的患者CPT水平升高,但接受奥沙利铂、紫杉醇和其他药物化疗后的患者CPT水平未见明显差异。结论：PV法可以定量地进行癌痛评估,有助于相对客观地进行癌痛分析。化疗后有明显神经病变的患者出现CPT升高,提示PV法具有潜在检测与评估化疗导致神经毒性的临床应用价值。     

Chemotherapy-induced neuropathy

Peripheral neuropathy is a common dose-limiting toxicity of chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) causes numerous debilitating symptoms, impairs functional capacity, and results in dose reductions or possible cessation of chemotherapy. Analgesic or neurotropic agents are only modestly effective in treating neuropathic symptoms. Animal and human studies into the pathogenesis of CIPN have demonstrated heterogeneity in the mechanism(s) of nerve injury caused by individual agents, which may partly explain the wide variation in the resultant symptoms. Development of optimal therapeutic measures to treat CIPN requires continued research into the pathophysiologic basis of nerve injury, identification of risk factors for individual patients, development of reproducible and easy-to-use measurement scales, and finally, the performance of appropriately designed clinical trials to evaluate potentially promising agents.     

Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN. Here, we discuss recent findings, which provide insight into this complex process of neuroimmune interactions. Findings show limited infiltration of leukocytes into the nervous system of CIPN animals and varying degrees of peripheral and central glial activation depending on the chemotherapeutic drug, dose, schedule, and timing. Most evidence suggests an increase in pro-inflammatory cytokine expression and changes in immune signalling pathways. There is, however, limited evidence available from human studies and it remains unclear whether neuroinflammatory responses are the cause of neuropathy or a bystander effect of the chemotherapy treatment.     

Chemotherapy-induced neurotoxicity in the treatment of gynecological cancers: State of art and an innovative approach for prevention

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm^® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.     

Beyond symptomatic relief for chemotherapy‐induced peripheral neuropathy: Targeting the source

Chemotherapy‐induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy‐induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism‐based, disease‐modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod‐shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy “currency” adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro‐oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro‐oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin‐μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti‐inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289‐98 . © 2018 American Cancer Society.     

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS)

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients’ daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2–3 weeks; test–retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS).The preliminary R-ODS did not meet Rasch model’s expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model’s expectations with proper validity and reliability, and was unidimensional.The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN.     

A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.

PURPOSE: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). EXPERIMENTAL DESIGN: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. RESULTS: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. CONCLUSIONS: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.     

瞬时受体电位通道在化疗所致周围神经病变中的研究进展

在患者使用抗癌药物过程中,化疗所致周围神经病变(chemotherapy-induced peripheral neuropathy, CIPN)的总体发生率高达100%,而CIPN的发生是一个极其复杂的病理过程,目前临床依旧缺乏有效的防治方法,因此寻找关键防治靶点迫在眉睫。越来越多的研究表明瞬时受体电位(transient receptor potential, TRP)通道与CIPN的发生和发展密切相关,有效阻断TRP通道能够抑制CIPN的发展进程,靶向TRP通道为治疗CIPN带来了新的切入点。因此,本文主要综述了TRP通道与CIPN的关系,以及靶向TRP通路用于防治CIPN的相关研究进展,希望能够为CIPN的临床防治提供新思路。     

Quantitative assessment of chemotherapy‐induced peripheral neurotoxicity using a point‐of‐care nerve conduction device

Chemotherapy‐induced peripheral neurotoxicity (CIPN) seriously impairs patients’ quality of life cumulatively and dose‐dependently. Because assessment of CIPN usually depends on patients’ subjective evaluation of symptoms, objective and quantitative measures are needed. We evaluated a point‐of‐care nerve conduction device (POCD), previously validated for the assessment of diabetic peripheral neuropathy. Sensory nerve action potential (SNAP) amplitude and sensory nerve conduction velocity (SNCV) of the sural nerve were measured using a portable, automated POCD (DPNCheck; NeuroMetrix Inc., Waltham, MA, USA) in patients with a clinical diagnosis of CIPN of grade 1 or higher. We compared SNAP and SNCV among patients with different grades of CIPN according to the Common Terminology Criteria for Adverse Events. A total of 50 patients (22 men, 28 women; median age, 64 years; grade 1/2/3, 21/18/11) were evaluated. Anticancer drugs responsible for CIPN were cisplatin in five patients, oxaliplatin in 15, carboplatin in 5, paclitaxel in 16, docetaxel in 14, nab‐paclitaxel in 7, vincristine in 6, and bortezomib in 3. Unadjusted SNAP was 8.45 ± 3.67 μV (mean ± SD) in patients with grade 1 CIPN, 5.42 ± 2.68 μV with grade 2, and 2.45 ± 1.52 μV with grade 3. Unadjusted SNCV was 49.71 ± 4.77 m/s in patients with grade 1 CIPN, 48.78 ± 6.33 m/s with grade 2, and 44.14 ± 7.31 m/s with grade 3. The adjusted SNAP after controlling for age significantly differed between each CTCAE grade (P < 0.001, ancova ). The adjusted SNCV after controlling for age and height also differed significantly (P = 0.027). Differences in the severity of CIPN could be detected objectively and quantitatively using this POCD.     

Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel

Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory–motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation ( P  = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.     

Peripheral neuropathy due to therapy with paclitaxel,gemcitabine, and cisplatin in patients with advanced ovarian cancer

Background: To evaluate the peripheral neuropathic changes induced by combination chemotherapy including paclitaxel (taxol), gemcitabine and cisplatin (TGC regimen). Patients and methods: Eighteen patients with primary or recurrent ovarian cancer were treated with paclitaxel 150 or 110mg/m², respectively, together with gemcitabine 800mg/m² and cisplatin 75mg/m², 3 weekly for 6 cycles.Neurologic evaluation and quantitative assessment by vibration perception threshold (VPT) and grip strength took place before therapy, after 3 and 6 cycles of chemotherapy, and thereafter when possible. Results: Both neuropathic symptoms and signs developed in all patients (100%), becoming most prominent 3 months after the last course of chemotherapy. Grade 3 peripheral neuropathy developed in one patient during chemotherapy, and in 3 additional patients after cessation of therapy.No significant differences were observed between chemo-naïve patients and pretreated patients. Conclusion: This TGC combination is well tolerated in terms of peripheral neuropathy during therapy, although the off-therapy worsening caused by cisplatin remains a problem.     

Meet the expert: How I treat chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent, often irreversible and disabling adverse effect of many commonly used chemotherapeutic agents. Older patients are at particular risk of developing CIPN due to comorbid conditions affecting the health of peripheral nerves. Symptoms of CIPN include paresthesias, dysesthesias, sensory loss, motor weakness, dysautonomia, and falls. Pharmacologic management of CIPN involves use of medications including antidepressants, anticonvulsants, and topical treatments for modulation of neuropathic pain. These medications should be used and monitored carefully in older patients as they may increase the risk of confusion, falls, and drug-drug interactions. Patients with CIPN are at an increased risk of falls and should be considered for supportive care interventions including physical and occupational therapy, assistive devices, and safety evaluations. Surveillance of CIPN during and following treatment is essential. The development of neuropathic symptoms may require dose reduction, drug holiday, or transitioning to another chemotherapeutic agent. Symptoms of CIPN typically improve following exposure to neurotoxic therapy, although in older adults the rate of improvement may be slow, and recovery is often incomplete. Early involvement of a neurologist should be considered in patients with atypical, progressive, motor- or autonomic- predominant presentations of neuropathy. Patients with refractory neuropathic pain or those who cannot tolerate standard symptomatic treatment should be referred to a pain specialist or palliative care.     

Pediatric chemotherapy induced peripheral neuropathy: A systematic review of current knowledge

BackgroundThe dramatic increase in the number of childhood cancer survivors over the last 60 years has made monitoring and minimising long term side effects of cancer treatment increasingly important. Chemotherapy induced peripheral neuropathy (CIPN) has been described with many commonly used chemotherapy agents. This article provides a critical overview of pediatric CIPN, its incidence, clinical manifestations, late effects, and recent advances in understanding of risk factors and pharmacogenomics as well as evaluating current assessment strategies and treatment approaches.MethodsNeurotoxicity data was systematically collated from Medline, Embase and Pubmed and analysed for quality, relevance and originality in three stages prior to inclusion. Quality scoring was done using the QUALSYST assessment tool.ResultsA total of 61 studies met inclusion criteria. Peripheral neuropathy is common and may be long lasting with characteristics specific to each chemotherapy agent. There is significant variability in reported incidence and natural history, related to challenges in clinical assessment and diagnosis. Emerging risk factors for CIPN include treatment factors such as dose, duration and concurrent medication and patient factors such as age and inherited susceptibilities. Recent identification of individual genetic variations has advanced understanding of pathomechanisms and may direct future treatment approaches.ConclusionWhile these studies guide suggestions for current clinical practice, further systematic research with development of strategies for amelioration and prevention of CIPN is necessary. Standardised assessment protocols and objective outcomes measures of CIPN applicable to patients of different ages are critical to enabling the development of novel treatments and facilitation of future clinical trials and treatment individualisation.     

Persistence of docetaxel-induced neuropathy and impact on quality of life among breast cancer survivors

BackgroundThis study evaluates persistence and severity of docetaxel-induced neuropathy (peripheral neuropathy (PN)) and impact on health related quality of life in survivors from early-stage breast cancer.MethodsOne thousand and thirty-one patients with early-stage breast cancer, who received at least one cycle of docetaxel and provided information on PN during treatment, completed questionnaires on PN as an outcome (Common Toxicity Criteria (CTC) scores, European Organisation for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC CIPN20) and EORTC Quality of Life Questionnaire (QLQ)-C30) after 1–3 years.FindingsUpon completion of docetaxel treatment, 241 patients (23%) reported PN, grades 2–4. PN persisted for 1–3 years among 81 (34%) while PN regressed to grades 0–1 among 160 (66%). Among 790 patients (77%) without PN, 76 (10%) developed PN 1–3 years later while 714 (90%) stayed free from PN. Significant risk factors for persistent PN were age ⩾55 (p = 0.001), maximum grade of PN during docetaxel treatment (p < 0.0001), persistent muscle and joint pain (p < 0.0001), stomatitis (p = 0.047) and fatigue (p = 0.001). Persistent PN had a significant negative correlation with health-related quality of life (HRQOL), functional scales and symptom scales.InterpretationsOverall, 15% of breast cancer survivors treated with docetaxel report PN 1–3 years after treatment with a significant negative impact on HRQOL.     

Examining the Impact of a Web-Based Intervention to Promote Patient Activation in Chemotherapy-Induced Peripheral Neuropathy Assessment and Management

Lack of activation in self-care can compromise a patient’s ability to monitor and manage cancer treatment-related side effects, such as chemotherapy-induced peripheral neuropathy (CIPN). The web-based Carevive® Care Planning System (CPS) was developed to promote evidence-based symptom assessment and treatment by enhancing patients’ involvement in their own care. The purpose of this single-arm, pre-test/post-test, prospective study was to examine whether the CPS can promote patient activation in CIPN symptom assessment and management. Seventy-five women with breast cancer receiving neurotoxic chemotherapy were recruited from a Comprehensive Cancer Center. Using standardized neuropathy measures embedded within the CPS, patients reported their CIPN symptoms over three consecutive clinical visits and completed the Patient Activation Measure (PAM) at the first and third visits. Mean changes in PAM scores between visits were compared using repeated measure analysis of covariance, adjusting for age. At baseline, patients were diagnosed with cancer within the past year (94.7%), highly activated (85% Level III/IV), and had a mean age of 51.3. PAM scores improved significantly from 67.15 (SD = 13.5; range = 47–100) at visit one to 69.29 (SD = 16.18; range = 47–100) (p = 0.02) (n = 62) at visit three. However, patients perceived the CPS to be of minimal value because it solely focused on CIPN and, for many, CIPN was not severe enough to motivate them to seek out symptom management information. Further research is needed to assess the utility of the CPS in promoting activation in the assessment and management of varying cancer treatment-related symptoms.     

Prophylaxe und Therapie der chemotherapieinduzierten Polyneuropathie

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most disabling side effects of cancer treatment with neurotoxic agents such as platinum compounds, taxanes, vinca-alkaloids, eribulin, and bortezomib. To protect patients from long-term impairments of daily functioning and quality of life, early diagnosis of CIPN via assessment of neuropathic symptoms and patient-reported outcome measures prior to each treatment cycle is desirable. Acute neurotoxicity due to oxaliplatin and taxane-induced acute pain syndrome are predictive for development of cumulative peripheral neurotoxicity. Prompt dose modification of the causal substance can avoid interruption or discontinuation of tumor therapy. Pharmacologic prophylaxis of CIPN has not been established so far. Duloxetine as well as exercise and balance training are promising approaches to CIPN treatment.