Management Of Chemotherapy-induced Peripheral Neuropathy Research Articles

An Integrative Review of the Effectiveness of Duloxetine Use in Cancer Patients Receiving Chemotherapy

Purpose: The objective of this Integrative Review of Literature (IRL) was to assess the efficacy of duloxetine in the management of chemotherapy-induced peripheral neuropathy (CIPN) among cancer patients. Peripheral neuropathy associated with chemotherapy manifests as symptoms such as tingling, burning, numbness, weakness, or pain in the hands and feet. The detrimental and, in some cases, debilitating impact of CIPN on individuals undergoing cancer treatment underscores the significance of investigating the effectiveness of duloxetine as part of the treatment plan for this condition. Procedure: A comprehensive literature search was performed to identify peer-reviewed journal articles on the effectiveness and safety of the use of duloxetine for the treatment of CIPN. The search was conducted using two electronic databases: CINHAL and PubMed. Additional supplemental sources, including the American Cancer Society, American Society of Clinical Oncology, Google Scholar, and Medline, were used to compile additional information for review. Results: The strengths and weaknesses of each article were reviewed utilizing the Johns Hopkins Research Appraisal tool. A data synthesis review exhibited good to high-quality articles with a range of evidence, including Level I, Level II, and Level III. Research yielded positive outcomes in reducing pain, increasing quality of life, and reducing the severity of symptoms for both physical and mental health with Duloxetine treatment. Results showed effectiveness and tolerability in the treatment of CIPN. Adding Duloxetine to the CIPN treatment plan positively impacted pain management and enhanced quality of life (QoL). Conclusion: Studies revealed that Duloxetine, as a pharmacologic intervention, resulted in a reduction in pain and an improvement in the quality of life (QoL) for patients experiencing chemotherapy-induced peripheral neuropathy (CIPN). Duloxetine demonstrated enhanced effectiveness, safety, and tolerability in its outcomes. Notably, the American Society of Clinical Oncology has designated Duloxetine as the standard of care for CIPN. Given its status as the standard of care, there is a higher likelihood of favorable considerations for Duloxetine by insurance companies.

CN104 Exercise interventions in the management of chemotherapy-induced peripheral neuropathy

CN104 Exercise interventions in the management of chemotherapy-induced peripheral neuropathy

Classical ayurveda management of TCH (taxane, carboplatin, and herceptin) based chemotherapy induced peripheral neuropathy- A case report

Although empirical data on the influence of Ayurveda on Chemo/Radiotherapy-induced side effects are limited, its methodological framework, grounded in a 'systems thinking' perspective, enables the precise delineation of the pathogenic stage of these side effects. This, in turn, facilitates the development of a strategy to address the decline in the quality of life parameters commonly associated with cancer treatment. Ayurveda personalized approach to disease management typically involves providing customized diets, lifestyle adjustments, medications, and detoxification therapies that target the entire body.We present a case involving a patient with numbness and pain in the right hand after undergoing chemotherapy who was referred to us by an oncologist for symptom management. This case report demonstrates the Ayurveda approach for establishing the etiology, pathogenesis, pathophysiology, and treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN) resulting from taxane-based chemotherapy. Following Ayurveda intervention, the patient exhibited significant improvements in symptoms and quality of life parameters.This case report systematically illustrates the application of Ayurveda approach in CIPN management.

Knowledge levels of oncology nurses regarding evidence-based practices in the assessment and management of chemotherapy-induced peripheral neuropathy

ObjectiveThe study aimed to determine the level of oncology nurses' knowledge of evidence-based practice for assessing and managing chemotherapy-induced peripheral neuropathy (CIPN). MethodsThis study employed a descriptive and cross-sectional research design. It was carried out with oncology nurses who were working at a university hospital in the Western Region of Turkey and who were members of the Oncology Nursing Association. The sample of the study consisted of 96 nurses who met the inclusion criteria. ResultsThe study sample comprised 94.8% female oncology nurses, 57.3% of whom held an undergraduate degree, and over half (58.5%) of whom were employed as clinical nurses. A majority of nurses (76.0%) indicated that they had not received any training in peripheral neuropathy. 35.4% of the nurses assessed patients receiving neurotoxic chemotherapy for peripheral neuropathy at each visit/each chemotherapy cycle. A total of 43.8% of nurses indicated that they frequently assessed patients for peripheral neuropathy at the conclusion of the treatment protocol. The oncology nurses assessed the patient-reported symptoms of motor neuropathy (58.3%), sensory neuropathy (56.3%), autonomic neuropathy (51.0%), neuropathic pain (55.2%), and co-occurring symptoms (52.1%) on a frequent basis. The nurses reported that they assessed muscle strength (56.3%), gait and balance (58.3%), and quality of life (52.1%) “frequently”. In contrast, they assessed deep tendon reflex (41.7%), neurological tests (36.5%), and social activities (46.8%) “rarely”. ConclusionsThe study findings indicated that oncology nurses require further education and training in evidence-based practices for the assessment and management of CIPN.

Chemotherapy-Induced Peripheral Neuropathy Impacts Quality of Life and Activities of Daily Living of Brazilian Multiple Myeloma Patients.

Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapyinduced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health- Related Quality of Life (HRQoL) and activities of daily living (ADL). We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Narrative Review and Proposed Theoretical Model.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating symptom experienced by cancer survivors. Despite the burden of CIPN-related symptoms, interventions remain limited. This narrative review seeks to propose a framework for CIPN predisposing, precipitating, and perpetuating factors (3Ps), which will provide a foundation for future research and clinical interventions aimed at mitigating CIPN-related symptoms and morbidity. A comprehensive literature search was performed using PubMed, guided by keywords related to "chemotherapy-induced peripheral neuropathy." Studies were limited to those with full text available in English. Predisposing factors outlined in this framework, such as older age and comorbid conditions, can be used to identify patients who have a higher risk of developing CIPN. The major precipitating factor of CIPN is the delivery of chemotherapy to peripheral nerves, which may be mitigated via cryotherapy or compression therapy during chemotherapy. Perpetuating factors can offer insight into psychological, cognitive, and behavioral modifications that could be treatment targets for CIPN management. The proposed 3P model can guide the development of effective interventions for CIPN by suggesting modifiable psychological and behavioral treatment targets that may mitigate the impact of CIPN for cancer patients.

The Potential Role of Ziziphus Jujube in the Management of Chemotherapy-Induced Peripheral Neuropathy

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a condition related to cancer treatment. Although various drugs and protocols are recommended for prophylactics and treatment, no strategies have yet been proven effective completely. Several drug treatment regimens have been proven for neuropathy, which includes calcium channel blockers, opioids, anti-depressants, and anticonvulsants, but they are only partially effective and have adverse effects associated with their administrations that diminish the quality of life and an economic burden is imposed on the patient. On the one hand, to treat peripheral neuropathy, a single therapeutic agent is not sufficient. On the other hand, Plants are the source of a vast number of bioactive phytochemicals which can potentially treat disease and related complications together

Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy are starting to be unraveled, namely in the supraspinal pain modulatory system. Based on our interests and experience in the field, we undertook a review of the brain-centered alterations that may underpin pain in CIPN. The changes in the descending pain modulation in CIPN models along with the functional and connectivity abnormalities in the brain of CIPN patients are analyzed. A translational analysis of preclinical findings about descending pain regulation during CIPN is reviewed considering the main neurochemical systems (serotoninergic and noradrenergic) targeted in CIPN management in patients, namely by antidepressants. In conclusion, this review highlights the importance of studying supraspinal areas involved in descending pain modulation to understand the pathophysiology of CIPN, which will probably allow a more personalized and effective CIPN treatment in the future.

Acupuncture for preventing progression of taxane-induced peripheral neuropathy (ATP): A phase II randomized, placebo-controlled trial.

TPS12154 Background: Chemotherapy-induced peripheral neuropathy (CIPN) from chemotherapy drugs such as taxanes can be detrimental to cancer survival, increasing the risk of falls and worsening physical functions. The current management of worsening and persistent CIPN during chemotherapy is dose reduction or discontinuation of chemotherapy. There is no effective treatment or preventative measure for CIPN. Methods: Trial design: The ATP trial is a two-arm, parallel, randomized controlled trial comparing weekly real acupuncture (RA) versus sham acupuncture (SA) during preplanned curative intent taxane containing regimens in patients with breast cancer. Eligibility criteria: English or Spanish-proficient; aged ≥18 years; histological diagnoses of invasive carcinoma of the breast; and plan to receive curative intent chemotherapy regimen containing paclitaxel or nab-paclitaxel weekly or biweekly as standard of care, developed CIPN grade ≥1 based on the NCI-CTCAE version 5.0, while receiving taxane; ≥ four weeks of paclitaxel or nab-paclitaxel weekly or biweekly planned, as standard of care and at treating physician’s discretion; willing to adhere to requirement that no new pain medication or dose changes be taken throughout the first 12 weeks of the study period; and willing to adhere to all study-related procedures. Specific aims: The primary aim is to evaluate the effectiveness of RA versus SA in preventing taxane-induced peripheral neuropathy progression as measured by Neuropathic Pain Scale (NPS) in patients with early-stage breast cancer who are receiving curative intent neurotoxic chemotherapy. The secondary aim is to evaluate the effectiveness of RA versus SA on chemotherapy relative dose intensity (RDI) and CIPN-related chemotherapy discontinuation. Statistical methods: We will randomize 80 patients, 40 to each arm. All randomized patients will be evaluable in the Intent to Treat (ITT) analyses because all will have completed the baseline assessment before randomization. We will use a linear mixed model (LMM) to compare the change in NPS between the arms from baseline to week 4. Based on our pilot data, a difference in CIPN grade from 1 to 2 corresponded to a difference in NPS from 12 to 22, a difference of ten points in 27 patients. The NPS standard deviation (SD) in patients with grade 1 CIPN was 17. With 80 patients we will have 80% power to detect a difference between arms as small as 10 points on the NPS, assuming a one-sided test, type I error of 5%, correlation between baseline and follow-up measurements of 0.5, SD of 17, and 15% attrition at week 4. Present accrual and target accrual: We accrued 43 participants in the intervention phase by the end of January 2024; the target accrual is 80 participants. Clinical trial information: NCT05458284 .

Abstract PO1-20-03: Acupuncture for Preventing Progression of Taxane-Induced PeripheralNeuropathy (ATP): A Phase II Randomized, Placebo Controlled Trial

Abstract Background: Chemotherapy-induced peripheral neuropathy (CIPN) from chemotherapy drugs such as taxanes can be detrimental to cancer survival, increasing the risk of falls and worsening physical functions. However, there is no effective treatment or preventative measure for CIPN. The current management of worsening and persistent CIPN during chemotherapy is dose reduction or discontinuation of chemotherapy. Our group previously completed a single-arm phase IIA pilot trial of women who developed National Cancer Institution Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade 2 CIPN during weekly paclitaxel for stage I-III breast cancer. The result suggested an acupuncture intervention for grade 2 CIPN might slow CIPN progression during chemotherapy. However, the role of acupuncture still needs to be better defined. Trial design: The ATP trial is a two-arm, parallel, randomized controlled trial comparing weekly real acupuncture (RA) versus sham acupuncture (SA) during preplanned curative intent taxane containing regimens in patients with breast cancer. The study will include two phases: screening and intervention. In the screening phase, eligible patients will consent and receive CIPN screening each week. Patients who develop grade 1 CIPN or higher based on NCI-CTCAE version 5.0 will be consented to the intervention phase and randomized to receive either weekly RA or SA using a standardized, semi-fixed protocol developed in our preliminary studies to improve CIPN pain. Eligibility criteria for the screening phase: English or Spanish-proficient; aged ≥18 years; histological diagnoses of invasive carcinoma of the breast; and plan to receive curative intent chemotherapy regimen containing paclitaxel or nab-paclitaxel weekly or biweekly as standard of care. Eligibility criteria for the intervention phase: in additional to the screening phase eligibility criteria, developed CIPN grade ≥1 based on the NCI-CTCAE version 5.0, while receiving taxane; ≥ four weeks of paclitaxel or nab-paclitaxel weekly or biweekly planned, as standard of care and at treating physician’s discretion; willing to adhere to requirement that no new pain medication or dose changes be taken throughout the first 12 weeks of the study period; and willing to adhere to all study-related procedures, including randomization to one of the two possible acupuncture treatments. Specific aims: The primary aim is to evaluate the effectiveness of RA versus SA in preventing taxane-induced peripheral neuropathy progression as measured by Neuropathic Pain Scale (NPS) in patients with early-stage breast cancer who are receiving curative intent neurotoxic chemotherapy. The secondary aim is to evaluate the effectiveness of RA versus SA on chemotherapy relative dose intensity (RDI) and CIPN-related chemotherapy discontinuation. Statistical methods: We will randomize 80 patients, 40 to each arm. All randomized patients will be evaluable in the Intent to Treat (ITT) analyses because all will have completed the baseline assessment before randomization. We will use a linear mixed model (LMM) to compare the change in NPS between the arms from baseline to week 4. Based on our pilot data, a difference in CIPN grade from 1 to 2 corresponded to a difference in NPS from 12 to 22, a difference of ten points in 27 patients. The NPS standard deviation (SD) in patients with grade 1 CIPN was 17. With 80 patients we will have 80% power to detect a difference between arms as small as 10 points on the NPS, assuming a one-sided test, type I error of 5%, correlation between baseline and follow-up measurements of 0.5, SD of 17, and 15% attrition at week 4. Present accrual and target accrual: We accrued 20 participants in the intervention phase by the end of June 2023; the target accrual is 80 participants. Contact information for people with a specific interest in the trial: W. Iris Zhi, MD, PhD, zhiw@mskcc.org. ClinicalTrails.gov Identifier: NCT05458284. Citation Format: W. Iris Zhi, Lauren Taylor, Raymond Baser, Matthew Weitzman, Qing Li, Christina Seluzicki, Ting Bao, Jun Mao. Acupuncture for Preventing Progression of Taxane-Induced PeripheralNeuropathy (ATP): A Phase II Randomized, Placebo Controlled Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-03.

Exercise intervention for the management of chemotherapy-induced peripheral neuropathy: a systematic review and network meta-analysis.

Although exercise is recommended for cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN), the effective types of exercise for preventing and treating CIPN remain unclear. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative effects of exercise on CIPN. We included relevant randomized controlled trials (RCTs) identified in a 2019 systematic review that evaluated the effects of exercise on CIPN and conducted an additional search for RCTs published until 2023. We evaluated the risk of bias for each RCT; the comparative effectiveness of exercise on patient-reported quality of life (QOL) through an NMA; and the effectiveness of exercise on QOL scores, patient-reported CIPN symptoms, and pain through additional meta-analyses. Twelve studies (exercise, n = 540; control, n = 527) comparing 8 exercise interventions were included in the analysis. All studies were determined to have a high risk of bias. The meta-analyses showed significantly improved QOL [standard mean differences (SMD) 0.45; 95% confidence interval (CI) = 0.12 to 0.78] and CIPN symptoms (SMD 0.46; 95% CI = 0.11 to 0.82). No severe adverse events were reported. Pain tended to improve with exercise (SMD 0.84; 95% CI = -0.11 to 1.80). An NMA suggested that the interventions of a combination of balance and strength training showed a significant improvement in QOL scores compared to the control. Exercise interventions may be beneficial for improving QOL and CIPN symptoms. High-quality large clinical trials and data are needed to conclude that exercise is beneficial and safe.

Neuroprotective Effect of Polyvalent Immunoglobulins on Mouse Models of Chemotherapy-Induced Peripheral Neuropathy.

The occurrence of neuropathic pain in chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting effect of many commonly-used anticancer agents. Polyvalent human immunoglobulins (hIg), used in the treatment of several peripheral neuropathies, may alleviate neuropathic pain. The aim of this project was to investigate the preventive effect of hIg in two mouse models of CIPN, induced by vincristine (VCR, 100 µg/kg/d) and oxaliplatin (OXP, 6 mg/kg/3d). Human Ig were administered one day before the first injection of chemotherapy. The onset of CIPN and effects of hIg were assessed via functional tests and morphological analyses of sensory nerves. To evaluate the effect of hIg on chemotherapy cytotoxicity, viability assays were performed using hIg (0 to 12 mg/mL) combined with anticancer agents on human cancer cell lines. The preventive treatment with hIg alleviated tactile hypersensitivity and nerve injuries induced by VCR. It also alleviated tactile/cold hypersensitivities and nerve injuries induced by OXP. Treatment with hIg did not affect the cytotoxicity of either chemotherapy. Furthermore, in combination with VCR, hIg potentiated chemo-induced cell death. In conclusion, hIg is a promising therapy to prevent the onset of CIPN and potentiate chemotherapy effect on cancer, reinforcing the interest in hIg in the management of CIPN.

αO-Conotoxin GeXIVA[1,2] Reduced Neuropathic Pain and Changed Gene Expression in Chronic Oxaliplatin-Induced Neuropathy Mice Model.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting painful neuropathy that occurs commonly during cancer management, which often leads to the discontinuation of medication. Previous studies suggest that the α9α10 nicotinic acetylcholine receptor (nAChR)-specific antagonist αO-conotoxin GeXIVA[1,2] is effective in CIPN models; however, the related mechanisms remain unclear. Here, we analyzed the preventive effect of GeXIVA[1,2] on neuropathic pain in the long-term oxaliplatin injection-induced CIPN model. At the end of treatment, lumbar (L4-L6) spinal cord was extracted, and RNA sequencing and bioinformatic analysis were performed to investigate the potential genes and pathways related to CIPN and GeXIVA[1,2]. GeXIVA[1,2] inhibited the development of mechanical allodynia induced by chronic oxaliplatin treatment. Repeated injections of GeXIVA[1,2] for 3 weeks had no effect on the mice's normal pain threshold or locomotor activity and anxiety-like behavior, as evaluated in the open field test (OFT) and elevated plus maze (EPM). Our RNA sequencing results identified 209 differentially expressed genes (DEGs) in the CIPN model, and simultaneously injecting GeXIVA[1,2] with oxaliplatin altered 53 of the identified DEGs. These reverted genes were significantly enriched in immune-related pathways represented by the cytokine-cytokine receptor interaction pathway. Our findings suggest that GeXIVA[1,2] could be a potential therapeutic compound for chronic oxaliplatin-induced CIPN management.

Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a treatment-limiting adverse effect of anticancer therapy that complicates the lifestyle of many cancer survivors. There is currently no gold-standard for the assessment or management of CIPN. Subsequently, understanding the underlying mechanisms that lead to the development of CIPN is essential for finding better pharmacological therapy. Therapy-induced senescence (TIS) is a form of senescence that is triggered in malignant and non-malignant cells in response to the exposure to chemotherapy. Recent evidence has also suggested that TIS develops in the dorsal root ganglia of rodent models of CIPN. Interestingly, several components of the senescent phenotype are commensurate with the currently established primary processes implicated in the pathogenesis of CIPN including mitochondrial dysfunction, oxidative stress, and neuroinflammation. In this article, we review the literature that supports the hypothesis that TIS could serve as a holistic mechanism leading to CIPN, and we propose the potential for investigating senotherapeutics as means to mitigate CIPN in cancer survivors.

Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design: Review. A thorough literature search was conducted using the terms 'dorsal root ganglion' and 'chemotherapy-induced peripheral neuropathy', along with appropriate variations. Searched databases included PubMed, EMBASE, Medline, Cochrane Library, Wiley Library, and Web of Science. Inclusion criteria targeted all English language, peer-reviewed original research from the inception of these databases to the present year. Review articles, book chapters, and other nonoriginal publications were excluded. Of 134 relevant studies identified, the majority were preclinical studies elucidating how various chemotherapeutic agents, especially taxanes, disrupt neurotransmission, inflammatory processes, and apoptotic pathways within sensory neurons of DRG. Not only do these effects correlate with the presentation of CIPN, but their disruption has also been shown to reduce CIPN symptoms in preclinical models. However, clinical studies addressing DRG interventions are very limited in number and scope at this time. These results reveal various pathways within DRG that may be effective targets for CIPN treatment. While limited, clinical studies do offer promise in the utility of DRG neuromodulation in managing painful CIPN. In the future, clinical trials are needed to assess interventions aimed at these neuronal and nonneuronal pathological targets to better treat this complex condition.

Safety and efficacy of cannabidiol in the management of chemotherapy-induced peripheral neuropathy.

12020 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting complication of cancer treatment that can negatively impact survival and quality of life. Cannabidiol (CBD) has been shown to attenuate CIPN in rodent models although its ability to reduce CIPN symptoms in humans is unexplored. Methods: A phase 3 randomized double-blind, placebo-controlled clinical trial was conducted between 6/1/2020 and 8/8/2022. Participants with nonmetastatic breast, colorectal, endometrial, and ovarian cancer (all stages) experiencing grade 2-3 CIPN (duration ≤ 2 years) were enrolled after completing taxane or platin-based chemotherapy. They were randomized into active and placebo groups, and followed x 16 weeks. The active group received 135 mg/day of CBD, provided as hemp-based whole plant extract in gelcaps, while placebo consisted of coconut oil gelcaps, delivered x 12 weeks. Participants were evaluated every 2 weeks using the EORTC QLQ-CIPN20, which assesses three categories of symptoms: sensory (numbness, tingling, pain), motor (weakness, difficulty walking), and autonomic (blurriness, hearing loss). Side effect and safety data were logged daily. Results: Of 230 participants with CIPN identified, 124 met eligibility, 54 consented and enrolled, and 46 completed ≥8 of the 12-week treatment phase and were included in the analysis. Mean age was 59.6 years; 89.1% were female. Of those participants, 63% had breast cancer, 19.6% colorectal, 15.2% ovarian, and 2.2% uterine. CIPN20 scores were summated and standardized. With placebo as the reference group, main effects for sensory and motor scales were adjusted for time from enrollment and baseline CIPN grade. Participants receiving CBD had greater improvement of sensory function (p=0.048), with reduced numbness and tingling, but without significant pain reduction (p=.282) or change in motor function (p=.158) vs placebo. No autonomic changes were observed. CBD was well tolerated without serious adverse events. Conclusions: CBD reduced numbness/tingling and improved sensory function vs. placebo, as assessed by the CIPN20 scale. These symptoms are among the most common and challenging symptoms of CIPN, for which there are limited available treatment options. However, CBD did not affect pain and motor function. Thus, this preliminary study provides evidence that CBD, dosed at 135 mg/day, might serve as a treatment for some CIPN symptoms without serious adverse events. Further research is needed to confirm these results and to assess the safety and efficacy of CBD combined with chemotherapy to prevent or attenuate CIPN. Such an advance could deliver a survival benefit by helping more people complete and better tolerate chemotherapy. Clinical trial information: NCT04398446 . [Table: see text]

Effect of proprioceptive neuromuscular facilitation technique and TENS on improving lower limb sensorimotor function, balance and quality of life in chemotherapy induced peripheral neuropathy in gynecological cancer: A randomized controlled trial protocol

Gynecological cancers are the most prevalent cancers in women, making it a significant public health concern. Chemotherapy drugs are an extremely effective approach for reducing cancer progression since they have various targets and mechanism of action focused at killing quickly multiplying cancer cells. Unfortunately, these drugs also affect normal cells and structures of the body, resulting in a variety of deleterious effects. Most common among them is chemotherapy induced peripheral neuropathy (CIPN). Taxanes, platinum medicines, vinca alkaloids and thalidomide are examples of popular pharmaceuticals that are prone to cause CIPN. When CIPN develops during active chemotherapy phase, it may result in the discontinuation or reduction of chemotherapy dose, which may render the dosage ineffective in cancer management. As a result, it is essential that physiotherapists investigate novel approaches to successfully manage the side effects that survivors must deal with. Here’s the idea we suggest by conducting a study which aim to assess the effectiveness of Proprioceptive Neuromuscular Facilitation Technique (PNF) with Transcutaneous Electrical Nerve Stimulation (TENS) and closed kinetic chain exercises with TENS on subjects with CIPN in Gynecological Cancer in two arm parallel superiority randomized control trial (RCT) on improving lower limb sensorimotor function, balance & quality of life. The total participants in the study will be divided into two equal groups and then the intervention will be given for 8 weeks to both the groups with 5 days in a week with 50 minute session each day. The results will be evaluated after 8 weeks of treatment and 3 weeks after completion of intervention for follow up. If the hypothesis of our study proves to be effective, this physiotherapy intervention could be included in management of CIPN. Along with it, it will help in reducing the rate of discontinuation of chemotherapy dose due to neuropathy.

Abstract P4-04-01: Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients

Abstract Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem that can be caused by some cytotoxic agents used in breast cancer (BC) treatment, most commonly seen following taxane-based therapy[1,2]. Several strategies have been studied for CIPN prevention and treatment, but, still, there is no standard recommendation, options are limited and results unsatisfactory [1]. Cryotherapy is a technique that consists of reducing the blood flow in a certain area of the body by cold temperatures, in order to limit the cytotoxic reach. A few studies have been conducted to analyze the safety and efficacy of this strategy in CIPN prevention and treatment, and results are controversial [3,4,5]. More data is needed to clarify cryotherapy role in this clinical context. Methods This is a retrospective analysis of 40 BC patients treated at a single Brazilian institution between December 2019 and June 2022, aiming at efficacy and safety of cryotherapy in the prevention and treatment of CIPN. Cryotherapy was administered by the Hilotherm Clinic Chemo HT02 device (Hilotherm GmbH - Oberwil bei Zug, Switzerland [6]). The procedure consisted of patients using glove and sock-like devices on hands and feet throughout the chemotherapy infusion. The devices were pre-cooled to 10oC and then put on patients 30 minutes before starting, till one hour after the end of chemotherapy infusion. A questionnaire, as proposed by Leonard et al [7], was administered to patients every cycle to assess the development and severity of CIPN symptoms. Statistical analyses were performed by using a Cox regression model. Results Of the 40 patients analysed, 33 (83.5%) underwent a taxane-based regimen. The median number of cryotherapy sessions was three (ranging from 1 to 12), and, when excluded patients who underwent only one session of cryotherapy, the median was 4 (range 2 to 12). 75% of the 40 patients underwent cryotherapy in all chemotherapy sessions, or were still receiving chemo with cryotherapy by the time of our analysis. 80% of those who left treatment did so after the first session (HR 40.44 (CI95: 8.34 – 196.1; p< 0.0001). CIPN was stable or better than the baseline status for 26 (87%) of the 30 patients that underwent more than 1 session of cryotherapy; only 1 (25%) of the four patients who developed CIPN worse than the baseline status had grade 2 symptoms. Conclusion Cryotherapy is a safe and tolerable strategy that can be used during chemotherapy for breast cancer. Our data suggests that this is an efficient approach to prevent and treat CIPN, but the retrospective nature of the study and the small sample size must be considered when interpreting the results. Finally, strategies must be developed to further improve adherence and tolerability, and prospective randomized trials are needed to confirm the efficacy of cryotherapy in this context. 1. Loprinzi et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol 38:3325-3348. 2020 2. Rivera et al. Chemotherapy-Associated Peripheral Neuropathy in Patients With Early-Stage Breast Cancer: A Systematic Review. JNCI J Natl Cancer Inst, 2018, Vol. 110, No. 2 3. Rosenbaek et al. Effect of cryotherapy on dose of adjuvant paclitaxel in early-stage breast cancer. Supportive Care in Cancer (2020) 28:3763–3769 4. Ruddy et al. Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial. The Breast Volume 48, December 2019 5. Shigematsu et al. Cryotherapy for the prevention of weekly paclitaxel-induced peripheral adverse events in breast cancer patients. Support Care Cancer. 2020 6. https://www.hilotherm.com/en/about-hilotherm/ accessed on July 15 2022 at 23:03 7. Leonard et al. Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer. BMC Cancer 2005, 5:116 Citation Format: Rafael B. Costa, Angélica Nogueira-Rodrigues, Claynner Paccely Oliveira Bessa, Rafaela Cristina Adalberto Menezes, Fernanda Coelho de Miranda Jorge Oliveira, Matheus Costa e Silva, Flávia Rocha Paes, Bruno L. Ferrari. Safety and efficacy of cryotherapy in the prevention and treatment of chemotherapy-induced peripheral neuropathy in breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-04-01.

Neurofilament light as a predictive biomarker of unresolved chemotherapy-induced peripheral neuropathy in subjects receiving paclitaxel and carboplatin

Management of chemotherapy-induced peripheral neuropathy (CIPN) remains a significant challenge in the treatment of cancer. Risk mitigation for CIPN involves preemptive reduction of cumulative dose or reduction of dose intensity upon emergence of symptoms, despite the risk of reduced tumor efficacy. A predictive biomarker for dose-limiting CIPN could improve treatment outcomes by allowing providers to make informed decisions that balance both safety and efficacy. To identify a predictive biomarker of CIPN, markers of neurodegeneration neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), tau and ubiquitin c-terminal hydrolase L1 (UCHL1) were assessed in serum of up to 88 subjects drawn 21 days following the first of 6 treatments with chemotherapeutics paclitaxel and carboplatin. Serum NfL and GFAP were increased with chemotherapy. Further, NfL change predicted subsequent onset of grade 2–3 CIPN during the remainder of the trial (mean treatment duration = 200 days) and trended toward stronger prediction of CIPN that remained unresolved at the end of the study. These results confirm previous reports that serum NfL is increased in CIPN and provide the first evidence that NfL can be used to identify subjects susceptible to dose-limiting paclitaxel and carboplatin induced CIPN prior to onset of symptoms.

Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurologic complication of chemotherapy, resulting in symptoms like pain, sensory loss, and numbness in the hands and feet that cause lots of uneasiness in patients with cancer. They often suffer from pain so severe that it interrupts the treatment, thus invalidating the entire chemotherapy-based healing process, and significantly reducing their quality of life. In this paper, we underline the role of the complement system in CIPN, highlighting the relevance of the C5a fragment and its receptor C5aR1, whose activation is thought to be involved in triggering a cascade of events that can lead to CIPN onset. Recent experimental data showed the ability of docetaxel and paclitaxel to specifically bind and activate C5aR1, thus shining light on one of the molecular mechanisms by which taxanes may activate a cascade of events leading to neuropathy. According to these new evidence, it was possible to suggest new mechanisms underlying the pathophysiology of CIPN. Hence, the C5a/C5aR1 axis may represent a new target for CIPN treatment, and the use of C5aR1 inhibitors can be proposed as a potential new therapeutic option to manage this high unmet medical need.