Showing papers on "Chemotherapy-induced peripheral neuropathy published in 2014"

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline

Abstract: Purpose To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors. Methods A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life. Results A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the ba...

Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition resulting from chemotherapy for cancer. Severe acute CIPN may require chemotherapy dose reduction or cessation. There is no effective CIPN prevention strategy; treatment of established chronic CIPN is limited, and the prevalence of CIPN is not known. Here we used a systematic review to identify studies reporting the prevalence of CIPN. We searched Embase, Medline, CAB Abstracts, CINAHL, PubMed central, Cochrane Library, and Web of Knowledge for relevant references and used random-effects meta-regression to estimate overall prevalence. We assessed study quality using the CONSORT and STROBE guidelines, and we report findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. We provide a qualitative summary of factors reported to alter the risk of CIPN. We included 31 studies with data from 4179 patients in our analysis. CIPN prevalence was 68.1% (57.7-78.4) when measured in the first month after chemotherapy, 60.0% (36.4-81.6) at 3months and 30.0% (6.4-53.5) at 6months or more. Different chemotherapy drugs were associated with differences in CIPN prevalence, and there was some evidence of publication bias. Genetic risk factors were reported in 4 studies. Clinical risk factors, identified in 4 of 31 studies, included neuropathy at baseline, smoking, abnormal creatinine clearance, and specific sensory changes during chemotherapy. Although CIPN prevalence decreases with time, at 6months 30% of patients continue to suffer from CIPN. Routine CIPN surveillance during post-chemotherapy follow-up is needed. A number of genetic and clinical risk factors were identified that require further study.

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

Abstract: Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN) remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review

Abstract: The objective of this study was to systematically review all available literature concerning chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QOL) among cancer patients. A computerized search of the literature was performed in December 2013. Articles were included if they investigated CIPN and QOL among cancer patients. Twenty-five articles were selected and were subjected to a 13-item quality checklist independently by two investigators. The methodological quality of the majority of the selected studies was adequate to high. The included studies differed tremendously with respect to study design (19 prospective studies, 5 cross-sectional, 1 both cross-sectional and prospective), patient population (lung, colorectal, ovarian, endometrial, cervical or breast cancer, lymphoma, acute lymphoblastic leukemia, or a mixed population), number of included patients (ranging from 14 to 1643), and ways to assess CIPN (objectively, subjectively, or both). Of the 25 included studies, 11 assessed the association of CIPN on patients’ QOL. While three of these studies did not find an association between CIPN and QOL, the others concluded that more CIPN was associated with a lower QOL. Although the included studies in this systematic review were very diverse, which impedes drawing firm conclusions on this topic, CIPN is likely to have a negative association with QOL. The variety of the studied patient populations and chemotherapeutic agents in the existing studies calls for further studies on this topic. These studies are preferably prospective in nature, include a large number of patients, and assess QOL and CIPN with validated questionnaires.

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature

Abstract: Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and therapeutic interventions.

The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) characterized by loss of sensory sensitivity and pain in hands and feet is the major dose-limiting toxicity of many chemotherapeutics. At present, there are no FDA-approved treatments for CIPN. The anti-diabetic drug metformin is the most widely used prescription drug in the world and improves glycemic control in diabetes patients. There is some evidence that metformin enhances the efficacy of cancer treatment. The aim of this study was to test the hypothesis that metformin protects against chemotherapy-induced neuropathic pain and sensory deficits. Mice were treated with cisplatin together with metformin or saline. Cisplatin induced increased sensitivity to mechanical stimulation (mechanical allodynia) as measured using the von Frey test. Co-administration of metformin almost completely prevented the cisplatin-induced mechanical allodynia. Co-administration of metformin also prevented paclitaxel-induced mechanical allodynia. The capacity of the mice to detect an adhesive patch on their hind paw was used as a novel indicator of chemotherapy-induced sensory deficits. Co-administration of metformin prevented the cisplatin-induced increase in latency to detect the adhesive patch indicating that metformin prevents sensory deficits as well. Moreover, metformin prevented the reduction in density of intra-epidermal nerve fibers (IENFs) in the paw that develops as a result of cisplatin treatment. We conclude that metformin protects against pain and loss of tactile function in a mouse model of CIPN. The finding that metformin reduces loss of peripheral nerve endings indicates that mechanism underlying the beneficial effects of metformin includes a neuroprotective activity. Because metformin is widely used for treatment of type II diabetes, has a broad safety profile, and is currently being tested as an adjuvant drug in cancer treatment, clinical translation of these findings could be rapidly achieved.

Chemotherapy dose reduction due to chemotherapy induced peripheral neuropathy in breast cancer patients receiving chemotherapy in the neoadjuvant or adjuvant settings: a single-center experience

Abstract: Purpose: Taxanes are a cornerstone treatment in early and advanced stage breast cancer and in other common solid tumor malignancies; however, the development of chemotherapy induced peripheral neuropathy (CIPN) often necessitates dose-reduction, which may hamper the effectiveness of the drug and compromise survival outcomes especially when used in the adjuvant setting. Limited literature is available on the prevalence and severity of dose reduction due to CIPN. We sought to determine the frequency and severity of CIPN-induced dose reduction in early stage breast cancer patients who received taxane-based chemotherapy in the neoadjuvant or adjuvant settings. Methods: We conducted a retrospective single-institution breast cancer clinic chart review of 123 newly diagnosed breast cancer patients and treated with taxane-based neoadjuvant/adjuvant chemotherapy at the University of Maryland Greenebaum Cancer Center between January 2008 and December 2011. Results: Forty-nine of 123 (40%; 95% CI: 31-49%) patients required dose reduction. Twenty-one (17%; 95% CI: 11-25%) of these patients were dose-reduced specifically due to CIPN that developed during treatment. The median relative dose intensity (received dose/planned dose) for the 21 CIPN-induced dose reduction patients was 73.4% (range, 68.0-94.0%). Patients with diabetes appeared to have a higher risk of taxane-induced dose reduction (p-value=0.01). African-American patients and those treated with paclitaxel (rather than docetaxel) experienced a higher-risk of CIPN-induced dose reduction (p-values are <0.001 and 0.001, respectively). Conclusions: The incidence of CIPN-associated dose reduction in our patient population was 17%. African-American patients, diabetics and subjects treated with paclitaxel had a higher risk for CIPN-associated dose reduction in our study.

A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70 % of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2 % ketamine plus 4 % amitriptyline (KA) cream for reducing CIPN. Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N = 462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average “pain, numbness, or tingling in [their] hands and feet over the past 24 h” on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N). The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference = −0.17, p = 0.363). This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.

A3 adenosine receptor agonist prevents the development of paclitaxel-induced neuropathic pain by modulating spinal glial-restricted redox-dependent signaling pathways.

Abstract: Chemotherapy-induced peripheral neuropathy accompanied by chronic neuropathic pain is the major dose-limiting toxicity of several anticancer agents including the taxane paclitaxel (Taxol). A critical mechanism underlying paclitaxel-induced neuropathic pain is the increased production of peroxynitrite in spinal cord generated in response to activation of the superoxide-generating enzyme, NADPH oxidase. Peroxynitrite in turn contributes to the development of neuropathic pain by modulating several redox-dependent events in spinal cord. We recently reported that activation of the Gi/Gq-coupled A3 adenosine receptor (A3AR) with selective A3AR agonists (ie, IB-MECA) blocked the development of chemotherapy induced-neuropathic pain evoked by distinct agents, including paclitaxel, without interfering with anticancer effects. The mechanism or mechanisms of action underlying these beneficial effects has yet to be explored. We now demonstrate that IB-MECA attenuates the development of paclitaxel-induced neuropathic pain by inhibiting the activation of spinal NADPH oxidase and two downstream redox-dependent systems. The first relies on inhibition of the redox-sensitive transcription factor (NFκB) and mitogen activated protein kinases (ERK and p38) resulting in decreased production of neuroexcitatory/proinflammatory cytokines (TNF-α, IL-1β) and increased formation of the neuroprotective/anti-inflammatory IL-10. The second involves inhibition of redox-mediated posttranslational tyrosine nitration and modification (inactivation) of glia-restricted proteins known to play key roles in regulating synaptic glutamate homeostasis: the glutamate transporter GLT-1 and glutamine synthetase. Our results unravel a mechanistic link into biomolecular signaling pathways employed by A3AR activation in neuropathic pain while providing the foundation to consider use of A3AR agonists as therapeutic agents in patients with chemotherapy-induced peripheral neuropathy.

Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial

Abstract: Chemotherapy-induced peripheral neuropathy is frequently a dose-limiting factor in cancer treatment and may cause pain and irreversible function loss in cancer survivors. We tested whether alpha-lipoic acid (ALA) could decrease the severity of peripheral neuropathy symptoms in patients undergoing platinum-based chemotherapy. Cancer patients 18 years or older were randomly selected to receive either 600 mg ALA or a placebo three times a day orally for 24 weeks while receiving chemotherapy regimens including cisplatin or oxaliplatin. Neuropathy was measured by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale and the NCI Common Toxicity Criteria for Adverse Events neurotoxicity grades. Results from timed functional tests and the Brief Pain Inventory (BPI) were secondary endpoints. Seventy of 243 (29 %) patients completed the study (24 weeks). Both the ALA and the placebo arms had a comparable drop-out rate. No statistically significant differences were found between the ALA and the placebo groups for FACT/GOG-Ntx scores, BPI scores, and patients' functional outcomes. This strategy of oral ALA administration was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. High attrition rates due to poor patient compliance and manner of dosage administration in this trial demonstrated a lack of feasibility for this intervention. Future studies to explore ALA as a neuroprotective agent should take heed of the barriers confronted in this study.

Prevention and treatment of chemotherapy-induced peripheral neuropathy.

Abstract: Purpose The prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) are reviewed. Summary A number of agents, including amifostine, glutathione, and vitamin E, were evaluated as prevention strategies for CIPN, with no agent demonstrating efficacy. Calcium and magnesium are effective for the prevention of CIPN; however, concerns regarding reduced chemotherapy efficacy linger. Venlafaxine, a serotonin–norepinephrine reuptake inhibitor (SNRI), was evaluated for the prevention of neuropathy in a randomized, double-blind, placebo-controlled Phase III trial of patients receiving an oxaliplatin-based regimens every two weeks and demonstrated significantly less acute neurotoxicity compared with the control group. Treatment options for CIPN include reducing the dosage of the chemotherapy, changing the chemotherapy, and treating CIPN with adjunct therapy. Adjunct therapy with topical agents, tricyclic antidepressants, and anticonvulsants, such as pregabalin and gabapentin, have shown limited efficacy. However, a randomized, double-blind, crossover, Phase III trial of duloxetine versus placebo for the treatment of CIPN caused by paclitaxel or oxaliplatin found that patients treated with duloxetine 60 mg daily had a larger average decrease in pain score than those receiving placebo, regardless of the chemotherapy used. Conclusion Calcium and magnesium infusions and venlafaxine are effective in preventing CIPN but are not routinely used because of concerns related to decreased chemotherapy efficacy. Adjunct treatment options for CIPN include a topical analgesic, a tricyclic antidepressant, an anticonvulsant, or an SNRI. Duloxetine is more effective than placebo in treating oxaliplatin- or paclitaxel-induced CIPN, is well tolerated, and should be considered to be a first-line treatment option for CIPN.

Rodent Models of Chemotherapy-Induced Peripheral Neuropathy

Abstract: Peripheral neuropathy is a common and dose-limiting side effect of many chemotherapeutic drugs. These include platinum compounds, taxanes, vinca alkaloids, proteasome inhibitors, and others such as thalidomide and suramin. Although many rodent models have been developed using either mice or rats, there is limited consistency in the dose or mode of delivery of the drug; the sex, age, and genetic background of the animal used in the study; and the outcome measures used in evaluation of the peripheral neuropathy. Behavioral assays are commonly used to evaluate evoked sensory responses but are unlikely to be a good representation of the spontaneous sensory paresthesias that the patients experience. Electrophysiologic tests evaluate the integrity of large myelinated populations and are useful in drugs that cause either demyelination or degeneration of large myelinated axons but are insensitive to degeneration of unmyelinated axons in early stages of neuropathy. Histopathologic tools offer an unbiased way to evaluate the degree of axonal degeneration or changes in neuronal cell body but are often time consuming and require processing of the tissue after the study is completed. Nevertheless, use of drug doses and mode of delivery that are relevant to the clinical protocols and use of outcome measures that are both sensitive and objective in evaluation of the length-dependent distal axonal degeneration seen in most chemotherapy-induced peripheral neuropathies may improve the translational utility of these rodent models.

North Central Cancer Treatment Group/Alliance trial N08CA—the use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy: A phase 3 randomized, double-blind, placebo-controlled study

Abstract: BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m2 glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN. Cancer 2014;120:1890–1897. © 2014 American Cancer Society.

Sequencing of charcot-marie-tooth disease genes in a toxic polyneuropathy

Abstract: Objective Mutations in Charcot-Marie-Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy—considered “acquired” in medical parlance—is unknown Chemotherapy induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable We used CIPN as clinical model to investigate the association of non-CMT polyneuropathy with CMT genes

Chemotherapy-induced peripheral neuropathy and impact on quality of life 6 months after treatment with chemotherapy

Abstract: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity of cytostatics With improved survival among cancer patients, CIPN may have a major impact on quality of life (QoL) of cancer survivors Objective: To determine the occurrence of CIPN induced by oxaliplatin and taxanes and its impact on QoL median 6 months after chemotherapy Methods: All patients who received their last treatment with oxaliplatin or taxanes in 2 consecutive years in the Maxima Medical Centre, the Netherlands, were eligible for the study Neurotoxicity and its effect on QoL was assessed with the recently developed Chemotherapy Induced Neurotoxicity Questionnaire (CINQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) median 6 months after cessation of therapy Results: Of the 58 eligible patients, 43 (741%) completed the questionnaire After a median follow-up of 65 months after cessation of therapy, most of the patients experienced neurotoxicity in the upper and lower extremities (788% and 897%, respectively) Overall, the most-reported complaints included numbness and tingling in hands as well as feet, suffering from cold feet, and trouble distinguishing objects in the hands Housekeeping difficulties were reported in 128% of patients, and 205% of patients became more dependent on others because of the neurotoxicity Overall, QoL was negatively affected by the impact of CIPN in 486% of patients Limitations: Due to the small sample size selection bias cannot be ruled out and no data about CIPN during treatment were available Conclusions After a median follow-up of 65 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL More research is needed to assess the impact of neurotoxicity on QoL Conclusions: After a median follow-up of 65 months after cessation of therapy with oxaliplatin or taxanes, CIPN is common and leads to impairment in patient QoL More research is needed to assess the impact of neurotoxicity on QoL KEYWORDS: cancer; chemotherapy; chemotherapy-induced peripheral neuropathy; neurotoxicity; oncology; quality of life

Genetic inactivation and pharmacological blockade of sigma-1 receptors prevent paclitaxel-induced sensory-nerve mitochondrial abnormalities and neuropathic pain in mice

Abstract: Background Paclitaxel, a widely-used antineoplastic drug, produces a painful peripheral neuropathy that in rodents is associated with peripheral-nerve mitochondrial alterations. The sigma-1 receptor (σ1R) is a ligand-regulated molecular chaperone involved in mitochondrial calcium homeostasis and pain hypersensitivity. This receptor plays a key role in paclitaxel-induced neuropathic pain, but it is not known whether it also modulates mitochondrial abnormalities. In this study, we used a mouse model of paclitaxel-induced neuropathic pain to test the involvement of the σ1R in the mitochondrial abnormalities associated with paclitaxel, by using genetic (σ1R knockout mice) and pharmacological (σ1R antagonist) approaches.

Comparison of two chemotherapy-induced peripheral neuropathy measurement approaches in children

Abstract: Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment in children; however, measurement of CIPN has been hampered by limitations in available tools, which may impact prevalence estimates. The purpose of this study was to assess the relative ability of the Common Terminology Criteria (CTCAE) rating process to detect sensory and motor neuropathy as compared to administration of the pediatric modified Total Neuropathy Score (peds-mTNS).

Management options for established chemotherapy-induced peripheral neuropathy.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a variety of chemotherapeutic agents. Clinicians are cognizant of the negative impact of CIPN on cancer treatment outcomes and patients' psychosocial functioning and quality of life. In an attempt to alleviate this problem, clinicians and patients try various therapeutic interventions, despite limited evidence to support efficacy of these treatments. The rationale for such use is mostly based on the evidence for the treatment options in non-CIPN peripheral neuropathy syndromes, as this area is more robustly studied than is CIPN treatment. In this manuscript, we examine the existing evidence for both CIPN and non-CIPN treatments and develop a summary of the best available evidence with the aim of developing a practical approach to the treatment of CIPN, based on available literature and clinical practice experience.

Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

Abstract: Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN) can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI) to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN) with those from healthy volunteers (HV). Twenty-four participants (n = 12 MM-CIPN, n = 12 HV) underwent Blood Oxygen Level-Dependent (BOLD) fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected). Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected). Significant positive correlation existed between the total neuropathy score (reduced version) and activation in the frontal operculum (close to insular cortex) during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87). Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

Evaluation of chemotherapy-induced peripheral neuropathy using current perception threshold and clinical evaluations.

Abstract: Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is increasing with introduction of new and combination cancer pharmacotherapies. This study evaluated associations between clinical and self-report measurements and current perception threshold (CPT), a neuroselective measure of sensory nerve function that may detect asymptomatic CIPN damage.

Chemotherapy-induced peripheral neuropathy in the adult.

Abstract: Purpose of review This review focuses on the newest data on mechanistic aspects of chemotherapy-induced peripheral neuropathy (CIPN), its assessment and the current status of neuroprotection and treatment options. Recent findings Several anticancer drugs are associated with CIPN. Rodent models showed that axons, dorsal root ganglia and terminal trees are affected, whereas myelin remains unaffected. Oxidative stress and mitochondrial damage, as well as the role of nerve growth factor, have been highlighted in CIPN. Candidate genes, single nucleotide polymorphisms, were correlated with a higher incidence of CIPN in patients receiving a combination of chemotherapies. CIPN assessment mainly relies on patient-oriented questionnaires, nevertheless an international effort is ongoing to access reliable and objective means to assess small and large fiber impairment.To date, dose modification is the most effective strategy to prevent CIPN, whereas duloxetine is recommended for patients with painful CIPN. Summary CIPN is a common, potentially severe and dose-limiting adverse effect of cancer treatment. Chemotherapies mainly target axons, dorsal root ganglia and terminal trees of intraepidermal nerve fibers. A quick and noninvasive method allowing the assessment of CIPN should be developed, although no treatment prevents CIPN or improves its long-term course. Furthermore, symptomatic therapy is often largely ineffective in reducing CIPN symptoms.

Acetyl- l -carnitine (ALCAR) for the prevention of chemotherapy-induced peripheral neuropathy in patients with relapsed or refractory multiple myeloma treated with bortezomib, doxorubicin and low-dose dexamethasone: a study from the Wisconsin Oncology Network

Abstract: Purpose Retreatment with bortezomib (B) is often considered for patients with relapsed multiple myeloma (MM), but this strategy is hindered by uncertainty of response and emergence of B-induced peripheral neuropathy (PN). We incorporated acetyl-l-carnitine (ALCAR) to prevent PN and allow for adequate dosing. We also investigated the correlation between B-inducible NF-κB activation and response to therapy.

Serotonin-Norepinephrine Reuptake Inhibitors for the Management of Chemotherapy-Induced Peripheral Neuropathy

Abstract: Objective: To review the literature evaluating serotonin-norepinephrine reuptake inhibitors (SNRIs) for chemotherapy-induced peripheral neuropathy (CIPN). Data Sources: A PubMed search (1966-January 2014) was performed using the key terms serotonin-norepinephrine reuptake inhibitor, desvenlafaxine, duloxetine, milnacipran, venlafaxine, chemotherapy, and peripheral neuropathy. Bibliographies of select articles were examined for additional references and abstracts. Study Selection and Data Extraction: Case reports and clinical trials published in English and conducted in humans were identified. All reports and trials evaluating a SNRI for the treatment of CIPN were included; 4 case reports, 1 open-label study, and 2 randomized controlled trials were identified for review. Data Synthesis: At present, no medications are approved for the treatment for CIPN. Emerging evidence suggests that venlafaxine and duloxetine may be effective for treating CIPN. Results of select trials report that these medications not o...

Chemotherapy induced peripheral neuropathy: the modified total neuropathy score in clinical practice

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, potentially reversible side effect of some chemotherapeutic agents. CIPN is associated with decreased balance, function and quality of life (QoL). This association has to date been under-investigated. To profile patients presenting with CIPN using the modified Total Neuropathy Score (mTNS) in this cross-sectional study and to examine the relationship between CIPN (measured by mTNS) and indices of balance, quality of life (QoL) and function. Patients receiving neurotoxic chemotherapy regimens were identified using hospital databases. Those who did not have a pre-existing neuropathy were invited to complete mTNS, Berg Balance Scale (BBS), timed up and go (TUG), and FACT-G QoL questionnaire. mTNS scores were profiled and also correlated with BBS, TUG and FACT-G using Spearmans correlation coefficient. A total of 29 patients undergoing neurotoxic chemotherapy regimens were tested. The patients mTNS scores ranged between 1 and 12 (median = 5), indicating that all patients had clinical evidence of neuropathy on mTNS. No significant correlations were found between mTNS and BERG (r = −0.29), TUG (r = 0.14), or FACT-G (r = 0.05). This study found a high prevalence of CIPN in patients treated with neurotoxic chemotherapy regimens. The mTNS provided a clinically applicable, sensitive screening tool for CIPN which could prove useful in clinical practice. mTNS did not correlate with BBS, TUG or FACT-G in this sample, possibly due to relatively mild levels of CIPN and consequent subtle impairments which were not adequately captured by gross functional assessments.

Efficacy and tolerability of controlled-release oxycodone for oxaliplatin-induced peripheral neuropathy and the extension of FOLFOX therapy in advanced colorectal cancer patients

Abstract: Background The oxaliplatin-based regimen FOLFOX is widely used to treat patients with advanced colorectal cancer (CRC). However, dose-limiting toxicity after continuous oxaliplatin administration can lead to peripheral neuropathy. Several agents, including opioids, that have been employed to treat oxaliplatin-induced peripheral neuropathy (OIPN) have been examined in clinical settings regarding their protective and therapeutic effects. However, the pharmacotherapy of these agents has not yet been established. Therefore, we investigated the efficacy and tolerability of oxycodone for OIPN and subsequently with FOLFOX therapy in CRC patients.