Prevention Of Peripheral Neuropathy Research Articles

Evaluation of the effect of pentoxifylline on the prevention of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study

BackgroundPaclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients.ResultsA simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity.ConclusionOral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly.Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535.

Structured Exercise Regimen in the Prevention of Peripheral Neuropathy in People with Type 2 Diabetes in a Low-Middle Income Country: An Open-Label, Randomized Controlled Trial

Structured Exercise Regimen in the Prevention of Peripheral Neuropathy in People with Type 2 Diabetes in a Low-Middle Income Country: An Open-Label, Randomized Controlled Trial

Recent advances in the treatment and prevention of peripheral neuropathy after multiple myeloma treatment.

The incidence of multiple myeloma (MM) is increasing year by year, requiring chemotherapy drugs to control the condition. With the advent of new proteasome inhibitors, immunomodulators, and monoclonal antibodies, the prognosis of patients has improved significantly. However, peripheral neuropathy caused by drugs limits the dose and duration of treatment, which seriously affects patients' quality of life and treatment outcome. Although the neuropathies induced by chemotherapy drugs have attracted much attention, their mechanism and effective prevention and treatment measures are not clear. Therefore, how to alleviate peripheral neuropathy caused by drugs for treatment of MM is a key issue in improving patients' quality of life and prolonging their survival time, which have some clinical value. In this paper, we review the current research on the pathogenesis, pharmacological and nonpharmacological treatment, and prevention, which expects to present instruction for peripheral neuropathy after treatment of MM.

A meta-analysis studying the utility of cryotherapy in the prevention of peripheral neuropathy in breast cancer patients receiving paclitaxel and nab-paclitaxel.

12025 Background: Debilitating Peripheral Neuropathy (PN) caused by paclitaxel adversely impacts the quality of life in Breast Cancer (BC) patients. Cryotherapy using cooling devices during taxane infusion is a non-invasive strategy to prevent PN, but its efficacy has not been established. We hope to answer this question through our meta-analysis. Methods: A systematic search with keywords and controlled vocabulary encompassing BC, antineoplastics, and paclitaxel was conducted in PubMed, CINHAL, Embase, Scopus, Web of Science Collections, and CENTRAL. All databases were searched on March 7, 2022. There were no search restrictions on date, language, status, or outcomes. 405 records were identified, and duplicates were removed using EndNote 20. The remaining 372 records were imported into Covidence, and the titles and abstracts were screened independently by 2 reviewers. 22 out of 63 full texts were relevant to our question of which 14 [12 Randomized control studies and 2 retrospective studies] were included for the meta-analysis using R package meta. Only studies that analyzed cryotherapy use in BC patients who received paclitaxel or nab-paclitaxel were included. Relative risk (RR) derived from random effects model with Mantel-Haenszel method was used to compare the occurrence of PN between cryotherapy vs placebo groups. Results: Pooled incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 PN was 24.85% (81/326) in the cryotherapy arm and 42.35% (72/170) in the placebo arm. Overall RR for CTCAE grade ≥ 2 PN with cryotherapy compared to placebo was 0.45 [0.27,0.77, p = 0.0031]. RR for sensory PN was 0.19 [0.05,0.66, p = 0.009] and for motor PN was 0.18 [0.03,0.99, p = 0.0491]. RR for Patient Neurotoxicity Questionnaire (PNQ) score ≥ D which connotes severe neuropathy was 0.24 [0.09,0.62, p = 0.0035]. Cold intolerance was the predominant adverse effect at 15% (37/247). Fingernail paronychia and skin irritation were reported at 0.8% (2/247) each. 5.1% (15/294) stopped cryotherapy use prior to completion. However, this number was driven by a single study (10/16 patients stopped using cryotherapy due to cold intolerance) and 7/11 studies had no discontinuations. Visual inspection of our funnel plots revealed no publication bias. Conclusions: Use of cryotherapy decreased the occurrence of CTCAE grade ≥ 2 PN by 55% in BC patients getting paclitaxel or nab-paclitaxel. Occurrence of both sensory and motor PN were lower. Cold intolerance was the most frequently reported issue with its use but lead to relatively low discontinuation rates in most studies. Given the lack of any severe adverse effect, cryotherapy use must be encouraged for patients receiving paclitaxel and nab-paclitaxel. Further studies are needed establish a standardized way of applying cryotherapy in terms of the device to use, timing and other logistical factors.

Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN.

Cryotherapy for the prevention of weekly paclitaxel-induced peripheral adverse events in breast cancer patients

PurposeThis randomized phase II study was conducted to investigate the efficacy of cryotherapy in preventing peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.MethodsPatients treated with 12 weekly doses of paclitaxel for breast cancer were randomized (1:1) into a cryotherapy or control group. The primary endpoint was the percentage of patients with a marked decrease in the Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-NTX) score. The secondary endpoints were Patient Neurotoxicity Questionnaire (PNQ), Common Terminology Criteria for Adverse Event (CTCAE) for peripheral neuropathy, and FACT-Taxane score.ResultsForty-four patients were randomly assigned to the cryotherapy (n = 22) or control groups (n = 22). The percentage of patients with a marked decrease in FACT-NTX scores was significantly lower in the cryotherapy group than in the control group (41 vs. 73%, p = 0.03). The incidence of CTCAE grade ≥ 2 sensory (p = 0.001) and motor peripheral neuropathy (p = 0.01), and PNQ grade D or higher for sensory peripheral neuropathy (p = 0.02), and decrease in the FACT-Taxane score (p = 0.02) were also significantly lower in the cryotherapy group than in the control group. There were no serious side effects associated with cryotherapy.ConclusionCryotherapy is an effective approach for prevention of peripheral neuropathy and dermatological adverse events in breast cancer patients treated with weekly paclitaxel.

Vitamin D insufficiency and risk of paclitaxel-induced peripheral neuropathy.

e12027 Background: Peripheral neuropathy (PN) is a severe, dose-limiting toxicity of paclitaxel that occurs in up to 25% of patients and can lead to permanent loss of balance and manual dexterity. Due to the lack of effective strategies for PN prevention or treatment, there is a critical need to identify predictive risk factors for paclitaxel-induced PN. Vitamin insufficiencies are known risk factors for PN in other disease states. However, the effect of vitamin insufficiency on paclitaxel-induced PN has not been adequately investigated. Methods: Baseline levels of vitamin D and other nutrients (vitamin B, homocysteine, folate) were measured, and PN was assessed weekly in an observational trial of patients receiving paclitaxel 80 mg/m2 for 12 weeks for non-metastatic breast cancer (NCT0233811). Nutrient levels were measured by Michigan Medicine and insufficiency defined by institutional standards (vitamin D insufficiency < 20 ng/mL). In the primary analysis, the maximum increase from baseline in the 8-item sensory subscale (ΔCIPN8) of the EORTC CIPN20, a validated patient-reported PN assessment tool, was compared in nutrient insufficient and sufficient patients. The effect of vitamin insufficiencies on PN-induced treatment disruptions (dose decrease, delay, or discontinuation) was conducted as a secondary analysis. Results: Only vitamin D insufficiency was identified in enough patients for analysis (15/37 = 41%). Vitamin D insufficient patients reported a greater mean (+/- SD) ΔCIPN8 (36.39 ±22.8) than vitamin D sufficient patients (16.29 ±16.3) (p = 0.003). However, the increase in treatment disruption for vitamin D insufficient patients was not significant (OR = 2.98, 95% CI [0.72, 12.34], p = 0.16). Conclusions: Paclitaxel-treated patients who were vitamin D insufficient at baseline had greater increases in patient-reported PN. If validated in larger studies, vitamin D insufficiency may be a clinically translatable, modifiable risk factor that can be used to prevent paclitaxel-induced PN in patients with non-metastatic breast cancer.

Clinical study of reduced glutathione in prevention of peripheral neuropathy caused by thalidomide

Objective To evaluate the efficacy of reduced glutathione(GSH) for preventing thalidomide-induced peripheral neuropathy (TiPN) in multiple myeloma (MM). Methods A total of 40 cases of MM in Jiading District Central Hospital Affiliated to Shanghai University of Medicine & Health Sciences from October 2014 to September 2016 were chosen as research objects. According to the randomized double blind principle, the patients were divided into two groups, the patients in the treatment group were treated with GSH and thalidomide in combination with chemotherapy, and the patients in the control group were treated without thalidomide and chemotherapy. The occurrence of TiPN between the two groups were observed and analyzed. Results The total incidence of TiPN in the treatment group was 25% (5/20), while that in the control group was 45% (9/20), there was no significant difference between the two groups (χ 2= 1.758, P > 0.05). There were no statistically significant differences in neuromotor conduction velocity (MCV), compound muscle action potential (CMAP) and sensory conduction velocity (SCV) between the two groups (all P > 0.05). There were no statistically significant difference in SNAP of median nerve and ulnar nerve between the two groups (both P > 0.05). But the sensory nerve action potential (SNAP) of superficial peroneal nerve in the treatment group was higher than that in the control group [(7.5±4.6) vs. (4.9±2.6)], and the difference was statistically significant (t= 2.221, P < 0.05). Conclusion GSH has a certain effect on the prevention of TiPN. Key words: Multiple myeloma; Peripheral nervous system diseases; Thalidomide; Glutathione

Amifostine pretreatment for patients with advanced colorectal cancer receiving folfox chemotherapy

19663 Background: Oxaliplatin plays a key role in the treatment of advanced colorectal cancer (CRC) but is associated with dose- limiting peripheral neuropathy (PN) in &gt;20% of patients. We investigated the effects of amifostine, a cytoprotective agent, on the prevention of PN in patients receiving oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOX) for the treatment of advanced (stage =III) CRC. Methods: In this ongoing prospective observational study, patients with stage =III CRC are assigned to receive FOLFOX alone (oxaliplatin 85 mg/m2, 5-FU 400 mg/m2 bolus, 5-FU 1.2 or 2.4 g/m2 continuous infusion over 46 h, LV 200 or 400 mg/m2) or FOLFOX plus 500 mg subcutaneous amifostine 30 minutes before chemotherapy. Some patients also receive bevacizumab and/or panitumumab. All patients receive Ca/Mg infusion (1 g each/100 mL normal saline) before and after oxaliplatin treatment. Incidence and degree of PN are assessed during biweekly patient interviews and graded using National Cancer Institute Common Toxicity Criteria Version 3. Results: Sixteen patients have enrolled to date (9 nonamifostine, 7 amifostine; mean age, 60.2 y [range, 33–81 y]; 81% men). Currently, data for 6 patients (3 per group) who have completed 12 cycles of therapy are available. Two of 3 patients in the nonamifostine group reported PN grade =2 during treatment; 1 of these patients required multiple treatment interruptions because of grade 3 PN. The third nonamifostine patient reported grade 1 PN on only 2 occasions during treatment but experienced grade 2 PN at 3-month follow-up. No patient in the amifostine group reported grade =2 PN during the treatment period. One amifostine patient required a reduction in oxaliplatin dose after 8 cycles because of neutropenia. At 3-month follow-up, 1 amifostine-treated patient reported grade 1 tingling in his hands and is currently receiving treatment with pregabalin. Conclusions: The use of amifostine for the prevention of oxaliplatin-induced PN is investigational. Patients with advanced CRC who received amifostine with FOLFOX chemotherapy had a decreased incidence and severity of PN compared with patients who did not receive amifostine. Updated data will be available at the time of presentation; study enrollment continues. No significant financial relationships to disclose.

The epidemiology of diabetic limb sepsis: an African perspective.

We review the epidemiology of foot and hand sepsis in adult diabetes patients in Africa. Limb sepsis in these patients is associated with significant morbidity and mortality. The pathogenesis of diabetic foot infections in these patient populations appears to be similar to that for patients in industrialized countries -ulcers and underlying peripheral neuropathy being the most important risk factors. Prevention of peripheral neuropathy through aggressive glycaemic control may be the most important primary control measure for foot infections. The tropical diabetic hand syndrome (TDHS) is being increasingly seen in diabetes patients in certain parts of Africa. The syndrome is acute, usually follows minor trauma to the hand, and is associated with a progressive synergistic form of gangrene. The major risk factors for TDHS are unknown but recent data suggest poor glycaemic control is associated with poor outcome. Treatment of TDHS requires aggressive surgery. Hence, preventive efforts for both foot and hand sepsis include aggressive glucose control, and education on hand and foot care and the importance of seeking medical attention promptly at the earliest onset of symptoms