Showing papers on "Chemotherapy-induced peripheral neuropathy published in 2020"

Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update

Abstract: PURPOSETo update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.METHODSAn...

Prevention of chemotherapy-induced peripheral neuropathy: A review of recent findings.

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

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Survivors: A Randomized Controlled Pilot Trial.

Abstract: Background Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population. Patients and methods Women with stage I-III breast cancer with grade 1 or higher CIPN after taxane-containing adjuvant chemotherapy were randomized 1:1 to an immediate acupuncture (IA) arm or to a waitlist control group (CG). Participants in the IA arm received 18 sessions of acupuncture over 8 weeks, then received no additional acupuncture. Patients in the CG arm received usual care over 8 weeks, followed by nine sessions of acupuncture over 8 weeks. Measures including Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy-Neurotoxicity subscale (FACT-NTX), and Brief Pain Inventory-short form (BPI-SF) were collected at baseline and at 4, 8, and 16 weeks after enrollment. Results Forty women (median age, 54) were enrolled (20 to IA and 20 to CG), with median time between completion of chemotherapy and enrollment of 14 months (range 1-92). At 8 weeks, participants in the IA arm experienced significant improvements in PNQ sensory score (-1.0 ± 0.9 vs. -0.3 ± 0.6; p = .01), FACT-NTX summary score (8.7 ± 8.9 vs. 1.2 ± 5.4; p = .002), and BPI-SF pain severity score (-1.1 ± 1.7 vs. 0.3 ± 1.5; p = .03), compared with those in the CG arm. No serious side effects were observed. Conclusion Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings. Implications for practice Chemotherapy-induced peripheral neuropathy (CIPN) is a toxicity that often persists for months to years after the completion of adjuvant chemotherapy for early breast cancer. In a randomized pilot trial of 40 breast cancer survivors with CIPN, an 8-week acupuncture intervention (vs. usual care) led to a statistically and clinically significant improvement in subjective sensory symptoms including neuropathic pain and paresthesia. Given the lack of effective therapies and established safety profile of acupuncture, clinicians may consider acupuncture as a treatment option for mild to moderate CIPN in practice.

Effect of Acupuncture vs Sham Procedure on Chemotherapy-Induced Peripheral Neuropathy Symptoms: A Randomized Clinical Trial.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common and debilitating long-term adverse effect of neurotoxic chemotherapy that significantly worsens cancer survivors’ quality of life. Well-tolerated, evidence-based interventions for CIPN are needed.1

Exercise Effects on Chemotherapy-Induced Peripheral Neuropathy: A Comprehensive Integrative Review.

Abstract: Background No effective cures for chemotherapy-induced peripheral neuropathy (CIPN) are known; however, exercise may be beneficial. Objective The purpose of this review was to synthesize high-quality research publications reporting the effects of exercise on CIPN and related outcomes among people of all age groups who received neurotoxic chemotherapy. Methods PubMed, CINAHL, Scopus, PsycINFO, and SPORTDiscus databases were searched first between May and November 2016 and then again in April 2019 for all clinical trials and meta-analyses. Subsequent hand-searching continued through April 2019. Potential scientific bias was rigorously evaluated, using the CONSORT (Consolidated Standards of Reporting Trials) guidelines. Results Thirteen studies (7 randomized controlled trials, 6 quasi-experiments) were found that reported exercise effects in various adult CIPN populations (ie, mixed cancer types and stages, chemotherapy regimens and status, and CIPN presence and severity). No studies provided high-quality evidence; 2 studies provided moderate-quality evidence. Most studies (76.3%) evaluated combined aerobic, strength, and balance training interventions of varying dosages. The most commonly improved outcomes were CIPN, balance, and fitness. All 7 studies with an aerobic exercise component led to significant-most studies showing moderate to large-CIPN benefits. Conclusions Few studies-none of high quality or in child/adolescent populations-have evaluated exercise effects on CIPN. The exercise interventions, dosages, and settings have been too heterogeneous to identify the most beneficial intervention for other CIPN-related outcomes. However, aerobic exercise may be a key component of exercise interventions for CIPN. Implications for practice Although promising, the empirical evidence is insufficient to definitively conclude that exercise interventions ameliorate CIPN.

Scrambler therapy for chemotherapy neuropathy: a randomized phase II pilot trial

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a prominent clinical problem, with limited effective therapies. Preliminary non-randomized clinical trial data support that Scrambler Therapy is helpful in this situation. Patients were eligible if they had CIPN symptoms for at least 3 months and CIPN-related tingling or pain at least 4/10 in severity during the week prior to registration. They were randomized to receive Scrambler Therapy versus transcutaneous electrical nerve stimulation (TENS) for 2 weeks. Patient-reported outcomes (PROs) were utilized to measure efficacy and toxicity daily for 2 weeks during therapy and then weekly for 8 additional weeks. This study accrued 50 patients, 25 to each of the 2 study arms; 46 patients were evaluable. There were twice as many Scrambler-treated patients who had at least a 50% documented improvement during the 2 treatment weeks, from their baseline pain, tingling, and numbness scores, when compared with the TENS-treated patients (from 36 to 56% compared with 16–28% for each symptom). Global Impression of Change scores for “neuropathy symptoms,” pain, and quality of life were similarly improved during the treatment weeks. Patients in the Scrambler group were more likely than those in the TENS group to recommend their treatment to other patients, during both the 2-week treatment period and the 8-week follow-up period (p < 0.0001). Minimal toxicity was observed. The results from this pilot trial were positive, supporting the conduct of further investigations regarding the use of Scrambler Therapy for treating CIPN.

A Comparative Review of Chemotherapy-Induced Peripheral Neuropathy in In Vivo and In Vitro Models:

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect caused by several classes of widely used anticancer therapeutics. Chemotherapy-induced peripheral neuropathy frequently leads to dose reduction or discontinuation of chemotherapy regimens, and CIPN symptoms can persist long after completion of chemotherapy and severely diminish the quality of life of patients. Differences in the clinical presentation of CIPN by widely diverse classifications of anticancer agents have spawned multiple mechanistic hypotheses that seek to explain the pathogenesis of CIPN. Despite its clinical relevance, common occurrence, and extensive investigation, the pathophysiology of CIPN remains unclear. Furthermore, there is no unequivocal gold standard for the prevention and treatment of CIPN. Herein, we review in vivo and in vitro models of CIPN with a focus on histopathological changes and morphological features aimed at understanding the pathophysiology of CIPN and identify gaps requiring deeper exploration. An elucidation of the underlying mechanisms of CIPN is imperative to identify potential targets and approaches for prevention and treatment.

Long-Term Prevalence of Sensory Chemotherapy-Induced Peripheral Neuropathy for 5 Years after Adjuvant FOLFOX Chemotherapy to Treat Colorectal Cancer: A Multicenter Cross-Sectional Study

Abstract: (1) Background: Oxaliplatin is among the most neurotoxic anticancer drugs. Little data are available on the long-term prevalence and consequences of chemotherapy-induced peripheral neuropathy (CIPN), even though the third largest population of cancer survivors is made up of survivors of colorectal cancer. (2) Methods: A multicenter, cross-sectional study was conducted in 16 French centers to assess the prevalence of CIPN, as well as its consequences (neuropathic pain, anxiety, depression, and quality of life) in cancer survivors during the 5 years after the end of adjuvant oxaliplatin chemotherapy. (3) Results: Out of 406 patients, the prevalence of CIPN was 31.3% (95% confidence interval: 26.8-36.0). Little improvement in CIPN was found over the 5 years, and 36.5% of patients with CIPN also had neuropathic pain. CIPN was associated with anxiety, depression, and deterioration of quality of life. None of the patients with CIPN were treated with duloxetine (recommendation from American Society of Clinical Oncology), and only 3.2%, 1.6%, and 1.6% were treated with pregabalin, gabapentin, and amitriptyline, respectively. (4) Conclusions: Five years after the end of chemotherapy, a quarter of patients suffered from CIPN. The present study showed marked psychological distress and uncovered a failure in management in these patients.

In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain.

Abstract: Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

Effectiveness of Acupuncture Treatment on Chemotherapy-Induced Peripheral Neuropathy: A Pilot, Randomized, Assessor-Blinded, Controlled Trial.

Abstract: Objective This pilot study aims to evaluate the effectiveness and safety of acupuncture in the treatment of chemotherapy-induced peripheral neuropathy (CIPN) Methods This study was a pilot randomized controlled trial, which was conducted with cooperation between Beijing University of Chinese Medicine (BUCM), China, and Tehran University of Medical Science (TUMS), Iran Forty participants with CIPN were randomly assigned (1 : 1) to receive twelve sessions of acupuncture (20 minutes each session over 4 weeks) or take one 300 mg tablet of vitamin B1 and three 300 mg capsules of gabapentin per day for 4 weeks, after which both groups were followed up for 4 weeks The primary endpoint was CIPN symptom severity measured by the Numerical Rating Scale (NRS) The secondary endpoints included sensory neuropathy grade evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE), neurophysiological assessment of CIPN by the nerve conduction study (NCS), and the patient overall satisfaction with treatment Safety was assessed at each visit Results The NRS and NCI-CTCAE sensory neuropathy grading scales decreased significantly over time in both groups (both P 005) Conclusion Our study revealed that acupuncture, as a kind of traditional Chinese therapeutic method, is significantly effective and safe in the treatment of CIPN Moreover, acupuncture is more effective than using vitamin B1 and gabapentin as the conventional treatment Trial registration This trial is registered with the Iranian Registry of Clinical Trials (IRCT20190615043900N1)

Recent advances in understanding chemotherapy-induced peripheral neuropathy.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN.

Painful and non-painful chemotherapy-induced peripheral neuropathy and quality of life in colorectal cancer survivors: results from the population-based PROFILES registry.

Abstract: This study aims to (1) examine the prevalence of painful versus non-painful chemotherapy-induced peripheral neuropathy (CIPN) among long-term colorectal cancer (CRC) survivors, (2) identify sociodemographic, clinical, and psychological factors associated with painful and non-painful CIPN, and (3) examine the associations of painful CIPN with health-related quality of life (HRQoL) in comparison with non-painful CIPN, i.e., numbness/tingling. All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors (n = 477) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30). Painful CIPN was reported by 9% (n = 45) of survivors and non-painful CIPN was reported by 22% (n = 103). Time since diagnosis was related to painful CIPN, and time since diagnosis, a higher disease stage, osteoarthritis, and more anxiety symptoms were related to non-painful CIPN. Finally, survivors with painful CIPN reported a worse global quality of life and worse physical, role, cognitive, and social functioning compared to survivors with non-painful CIPN and those without any sensory CIPN. No differences were found between survivors with non-painful CIPN and those without sensory CIPN. It seems that painful CIPN must be distinguished from non-painful CIPN, as only painful CIPN was related to a worse HRQoL. Future research is needed to examine whether painful CIPN must be distinguished from non-painful CIPN regarding predictors, mechanisms, and treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87–2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8–27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Reporting of paclitaxel-induced peripheral neuropathy symptoms to clinicians among women with breast cancer: a qualitative study.

Abstract: Cases of chemotherapy-induced peripheral neuropathy (CIPN) under-reporting have been sporadically described in the literature, but no studies have focused on actively examining this behavior. Our primary aim was to identify women who purposefully under-reported CIPN, along with reasons for doing so. A secondary aim was to explore factors enabling or hindering communication of CIPN to clinicians. Semi-structured interviews were conducted with women with breast cancer who had received paclitaxel in a prospective observational study. The interview guide was developed based on factors hypothesized to influence side effect disclosure to clinicians. Interviews were recorded, transcribed verbatim, and thematically content analyzed. Thirty-four women were interviewed. Three main themes emerged from the analysis: (1) enablers of CIPN reporting (e.g., positive relationship with the oncology team, sufficient appointment time, existence of alternative communication channels to office visits, expectation of CIPN as a side effect); (2) deterrents to CIPN reporting (e.g., perception of need to complete the full course of therapy, fear of treatment discontinuation, lack of knowledge of long-term consequences of CIPN); and (3) balancing survival versus functional impairment due to CIPN. Women prioritized efficacy over CIPN until physical functioning was meaningfully affected. No patients reported purposeful CIPN under-reporting, but three women admitted having considered doing so. Despite the lack of evidence of CIPN withholding, women considered both the effectiveness and the toxicity of paclitaxel treatment, as well as beliefs about treatment and long-term consequences of CIPN and relationship with the oncology team, when deciding whether to report CIPN symptoms.

An Exploratory Randomized Trial of Physical Therapy for the Treatment of Chemotherapy-Induced Peripheral Neuropathy:

Abstract: Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxane treatment and cannot currently be prevented or adequately treated. Physical therapy is often used for neural rehabilitation following injury but has not been evaluated in this patient population. Methods. Single-blind, randomized controlled exploratory study compared standard care to a physical therapy home program (4 visits) throughout adjuvant taxane chemotherapy for stage I-III patients with breast cancer (n = 48). Patient questionnaires and quantitative sensory testing evaluated the treatment effect throughout chemotherapy to 6 months post treatment. Nonrandomized subgroup analysis observed effect of general exercise on sensory preservation comparing those reporting moderate exercise throughout chemotherapy to those that did not exercise regularly. Clinical Trial Registration. clinicaltrials.gov (NCT02239601). Results. The treatment group showed strong trends toward less pain (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-1.01; P = .053) and pain decreased over time (OR 0.85, 95% CI 0.76-0.94; P = .002). Pain pressure thresholds (P = .034) and grip dynamometry (P < .001) were improved in the treatment group. For the nonrandomized subgroup analysis, participants reporting general exercise had preservation of vibration (Left P = .001, Right P = .001) and normal heat pain thresholds (Left P = .021, Right P = .039) compared with more sedentary participants. Conclusion. Physical therapy home program may improve CIPN pain in the upper extremity for patients with breast cancer, and general exercise throughout chemotherapy treatment was observed to have correlated to preservation of sensory function. Further research is required to confirm the impact of a physical therapy home program on CIPN symptoms.

A Pilot Randomized Sham-Controlled Trial of MC5-A Scrambler Therapy in the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy (CIPN).

Abstract: Background:Chemotherapy-induced peripheral neuropathy (CIPN) affects 30% to 40% of patients with cancer with long-lasting disability. Scrambler therapy (ST) appeared to benefit patients in uncontro...

The Utility of Corneal Nerve Fractal Dimension Analysis in Peripheral Neuropathies of Different Etiology.

Abstract: Purpose Quantification of corneal confocal microscopy (CCM) images has shown a significant reduction in corneal nerve fiber length (CNFL) in a range of peripheral neuropathies. We assessed whether corneal nerve fractal dimension (CNFrD) analysis, a novel metric to quantify the topological complexity of corneal subbasal nerves, can differentiate peripheral neuropathies of different etiology. Methods Ninety patients with peripheral neuropathy, including 29 with diabetic peripheral neuropathy (DPN), 34 with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 with chemotherapy-induced peripheral neuropathy (CIPN), 14 with human immunodeficiency virus-associated sensory neuropathy (HIV-SN), and 20 healthy controls (HCs), underwent CCM for estimation of corneal nerve fiber density (CNFD), CNFL, corneal nerve branch density (CNBD), CNFrD, and CNFrD adjusted for CNFL (ACNFrD). Results In patients with DPN, CIDP, CIPN, or HIV-SN compared to HCs, CNFD (P = 0.004-0.0001) and CNFL (P = 0.05-0.0001) were significantly lower, with a further significant reduction among subgroups. CNFrD was significantly lower in patients with CIDP compared to HCs and patients with HIV-SN (P = 0.02-0.0009) and in patients with DPN compared to HCs and patients with HIV-SN, CIPN, or CIDP (P = 0.001-0.0001). ACNFrD was lower in patients with CIPN, CIDP, or DPN compared to HCs (P = 0.03-0.0001) and in patients with DPN compared to those with HIV-SN, CIPN, or CIDP (P = 0.01-0.005). Conclusions CNFrD can detect a distinct pattern of corneal nerve loss in patients with DPN or CIDP compared to those with CIPN or HIV-SN and controls. Translational relevance Various peripheral neuropathies are characterized by a comparable degree of corneal nerve loss. Assessment of corneal nerve topology by CNFrD could be useful in differentiating neuropathies based on the pattern of loss.

Yoga for Chemotherapy-Induced Peripheral Neuropathy and Fall Risk: A Randomized Controlled Trial.

Abstract: Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect that worsens quality of life and increases the risk of falls in cancer survivors. Evidence of yoga's safety and efficacy in treating CIPN is lacking. Methods In a randomized controlled study, we assigned breast and gynecological cancer survivors with persistent moderate-to-severe CIPN pain, numbness, or tingling with a score of 4 or greater (0-10 numeric rating scale [NRS]) for at least 3 months after chemotherapy to 8 weeks of usual care or yoga focused on breathwork and musculoskeletal conditioning. Primary endpoint was treatment arm differences for NRS, and secondary endpoints were Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx), and Functional Reach Test after week 8. We tested treatment arm differences for each outcome measure using linear mixed models with treatment-by-time interactions. All statistical tests were two-sided. Results We randomly assigned 41 participants into yoga (n = 21) or usual care (n = 20). At week 8, mean NRS pain decreased by 1.95 points (95% confidence interval [CI] = -3.20 to -0.70) in yoga vs 0.65 (95% CI = -1.81 to 0.51) in usual care (P = .14). FACT/GOG-Ntx improved by 4.25 (95% CI = 2.29 to 6.20) in yoga vs 1.36 (95% CI = -0.47 to 3.19) in usual care (P = .035). Functional reach, an objective functional measure predicting the risk of falls, improved by 7.14 cm (95% CI = 3.68 to 10.59) in yoga and decreased by 1.65 cm (95% CI = -5.00 to 1.72) in usual care (P = .001). Four grade 1 adverse events were observed in the yoga arm. Conclusion Among breast and gynecological cancer survivors with moderate-to-severe CIPN, yoga was safe and showed promising efficacy in improving CIPN symptoms.

High mobility group box-1-toll-like receptor 4-phosphatidylinositol 3-kinase/protein kinase B-mediated generation of matrix metalloproteinase-9 in the dorsal root ganglion promotes chemotherapy-induced peripheral neuropathy.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutics. The mechanisms of CIPN remain substantially unidentified, although inflammation-induced peripheral sensitization has been indicated as an important factor. Here, we aimed to illustrate the role of the matrix metalloproteinase (MMP)-9-related signaling pathway in the process of CIPN. Oxaliplatin (L-OHP) was administered to mice to establish the CIPN model. Gelatin zymography was used to measure MMP-9/2 activities. Western blotting and immunohistochemistry were used to measure the expression of high-mobility group box-1 (HMGB-1), calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1. Mechanical withdrawal was measured by von Frey hairs testing. Raw 264.7 cells and SH-SY5Y cells were cultured to investigate cell signaling in vitro. Here, we report that L-OHP-induced mechanical pain in mice with significant MMP-9/2 activation in dorsal root ganglion (DRG) neurons. MMP-9 inhibition or knockout alleviated the occurrence of CIPN directly. MMP-9/2 were released from macrophages and neurons in the DRG via the HMGB-1-toll-like receptor 4 (TLR4)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) axis, because MMP-9/2 activities could be reduced by macrophage scavengers or PI3Kγ knockout in CIPN mice. The in vitro data revealed that induced MMP-9 activity by recombinant HMGB-1 could be abolished by TLR4, PI3K or Akt inhibitors. Finally, it was shown that N-acetyl-cysteine (NAC) could reduce MMP-9/2 activities and attenuate CIPN effectively and safely. The HMGB-1-TLR4-PI3K/Akt-MMP-9 axis is involved in the crosstalk between macrophages and neurons in the pathological process of CIPN in mice. Direct inhibition of MMP-9 by NAC may be a potential therapeutic regimen for CIPN treatment.

Efficacy and Safety of Acupuncture against Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Abstract: Objective To determine the effectiveness and safety of acupuncture for chemotherapy-induced peripheral neuropathy. The review has been registered on the "PROSPERO" website; the registration number is CRD42020151654. Methods A comprehensive literature search was performed on 7 electronic databases from the time of inception to March 2020. RCTs studies on acupuncture for CIPN compared with medication or sham acupuncture were included. Statistical analysis was carried out using RevMan 5.3. Results In total, 19 RCTs covering 1174 patients were enrolled. The results showed that acupuncture significantly increased the effective rate of CIPN compared with medicine and sham acupuncture. And acupuncture had a good effect on the recovery of nerve conduction velocity and improving pain. Among the acupoints involved in the treatment of CIPN, LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie) were the most commonly used. Conclusion The use of acupuncture in the management of CIPN is safe and effective. The most used acupoints for CIPN are LI4, LI11, ST36, EX10 (Bafeng), and EX-UE 9 (Baxie).

The Physical Consequences of Chemotherapy-Induced Peripheral Neuropathy.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of numerous chemotherapy drugs. CIPN negatively impacts function and quality of life during and after treatment. We will provide a review of the data describing the physical consequences of CIPN and discuss the possible long term impact on emotional well-being and quality of life. CIPN negatively affects physical function and many aspects of quality of life. Exercise interventions are likely to reduce the risk of falls associated with CIPN. There remains a need for evidence-based interventions focused on improving symptoms, function, and quality of life in persons with CIPN.

P-Glycoprotein Inhibition Exacerbates Paclitaxel Neurotoxicity in Neurons and Patients With Cancer

Abstract: Paclitaxel-induced peripheral neuropathy (PIPN) is a common and dose-limiting adverse event. The role of P-glycoprotein (P-gp) in the neuronal efflux of paclitaxel was assessed using a translational approach. SH-SY5Y cells were differentiated to neurons and paclitaxel toxicity in the absence and presence of a P-gp inhibitor was determined. Paclitaxel caused marked dose-dependent toxicity in SH-SY5Y-derived neurons. Paclitaxel neurotoxicity was exacerbated with concomitant P-gp inhibition by valspodar and verapamil, consistent with increased intracellular accumulation of paclitaxel. Patients with cancer treated with paclitaxel and P-gp inhibitors had a 2.4-fold (95% confidence interval (CI) 1.3-4.3) increased risk of peripheral neuropathy-induced dose modification while a 4.7-fold (95% CI 1.9-11.9) increased risk for patients treated with strong P-gp inhibitors was observed, and a 7.0-fold (95% CI 2.3-21.5) increased risk in patients treated with atorvastatin. Atorvastatin also increased neurotoxicity by paclitaxel in SH-SY5Y-derived neurons. Clinicians should be aware that comedication with P-gp inhibitors may lead to increased risk of PIPN.

Chemotherapy-induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design.

Abstract: Background To the authors' knowledge, the empiric identification of agents and interventions to mitigate chemotherapy-induced peripheral neuropathy (CIPN) has resulted in only 1 agent that modestly mitigates it and no agents or interventions that prevent its development. This speaks to the need for a mechanistic understanding of CIPN to develop effective interventions. Methods To understand the extent to which mechanistic understanding of CIPN is being translated into the development of interventions, the National Cancer Institute conducted a review of the National Institutes of Health (NIH)'s portfolio of investigator-initiated grants, the literature regarding CIPN mechanisms, and the clinical trials listed in the ClinicalTrials.gov database from January 1, 2011, to May 22, 2019. Results A total of 69 NIH-supported grants and 95 published articles were identified that evaluated mechanistic pathways of 7 different chemotherapy agents that cause CIPN. The review also identified 35 clinical trials that investigated agents or devices with which to treat CIPN. Only 3 trials incorporated a mechanistic rationale to support the choice of the intervention. Conclusions To the authors' knowledge, very little of the mechanistic understanding of the development of CIPN is being translated into intervention rationale in clinical trials that evaluate interventions to mitigate CIPN. Efforts to incentivize this translation are needed.