Showing papers on "Chemotherapy-induced peripheral neuropathy published in 2009"
TL;DR: The best approach is to treat symptomatically, and to start with broad‐spectrum analgesic medications such as non‐steroidal anti‐inflammatory drugs (NSAIDs), if NSAIDs fail, a reasonable second‐line agent in properly selected patients may be an opioid.
Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is still a common and disabling side effect of many chemotherapy agents in use today. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful yet. This review will discuss the diagnosis and evaluation of neuropathy in cancer patients, as well as reviewing the various prophylactic and symptomatic treatments that have been proposed or tried. However, sufficient evidence is lacking to recommend any of these treatments to patients suffering with CIPN. Therefore, the best approach is to treat symptomatically, and to start with broad-spectrum analgesic medications such as non-steroidal anti-inflammatory drugs (NSAIDs). If NSAIDs fail, a reasonable second-line agent in properly selected patients may be an opioid. Unfortunately, even when effective in other types of neuropathic pain, anti-depressants and anticonvulsants have not yet proven effective for treating the symptoms of CIPN.
171 citations
TL;DR: Although overall motor function was below population norms on the BOT‐2, presence of neuropathy did not significantly correlate with motor functional status or QOL, and its impact on motor function and quality of life (QOL) among children who survived ALL.
Abstract: Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Recent advances in treatment have led to dramatically improved survival rates. Standard ALL treatment includes multiple administrations of the chemotherapeutic drug vincristine, which is a known neurotoxic agent. Although peripheral neuropathy is a well-known toxicity among children receiving vincristine acutely, the long-term effects on the peripheral nervous system in these children are not clear. The objective of this study was to determine the prevalence of neuropathy and its impact on motor function and quality of life (QOL) among children who survived ALL. Thirty-seven survivors of childhood ALL aged 8–18 underwent evaluation for neuropathy through self-reported symptoms, standardized examinations, and nerve conduction studies (NCS). Functional impact of neuropathy was assessed using the Bruininks-Oseretsky test of Motor Proficiency (BOT-2). QOL was assessed using the PedsQL. Nerve conduction study abnormalities were seen in 29.7% of children who were longer than 2 years off therapy for ALL. Most children with an abnormal examination or NCS did not have subjective symptoms. Although overall motor function was below population norms on the BOT-2, presence of neuropathy did not significantly correlate with motor functional status or QOL.
131 citations
TL;DR: An in vitro compartmentalized microfluidic culture system is developed to examine the site of toxicity of chemotherapeutic drugs and shows that recombinant human erythropoietin, which had been shown to be neuroprotective against paclitaxel neurotoxicity, provides neuroprotection whether it is applied to the cell body or the axons directly.
124 citations
TL;DR: It is confirmed that CIPN is a predictor of NP, suggesting that survivors treated with paclitaxel should be regularly monitored for NP beyond treatment, and research into symptoms that persist after treatment is important.
93 citations
TL;DR: The Patient Neurotoxicity Questionnaire appears to be more sensitive and responsive than the NCI-CTC for CIPN; the PNQ appears to have diagnostic validity for evaluating CIPn in patients who are receiving neurotoxic chemotherapy.
Abstract: The aim of this study was to prospectively evaluate chemotherapy-induced peripheral neuropathy (CIPN) using a patient-based instrument, the Patient Neurotoxicity Questionnaire (PNQ) and a physician-based instrument, the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) in patients with advanced or metastatic breast cancer who were treated with weekly paclitaxel. CIPN symptoms were prospectively assessed in 35 patients using the PNQ, NCI-CTC, and the Functional Assessment of Cancer Therapy (FACT)-Taxane including neurotoxicity component (Ntx) at the baseline, and 8 and 16 weeks after starting chemotherapy. For sensory neuropathy symptoms, the reported incidence of CIPN was significantly increased during active treatment in terms of both the PNQ and NCI-CTC assessments. In contrast, there was a notable increase of patient motor neuropathy symptoms that were elucidated only by the PNQ. The PNQ grades of CIPN were widely distributed in the patient population as compared with the NCI-CTC grades for both sensory and motor neuropathy. The sensory PNQ grade was correlated with sensory NCI-CTC grade (r = 0.58) and Ntx (r = 0.51), and the motor PNQ grade was correlated with Ntx (r = 0.57). The PNQ appears to be more sensitive and responsive than the NCI-CTC for CIPN; the PNQ appears to have diagnostic validity for evaluating CIPN in patients who are receiving neurotoxic chemotherapy.
51 citations
TL;DR: Empirical evidence is provided on the importance CIPN as a risk factor for NP in breast cancer patients and how it is associated with cummulative dose of paclitaxel, and comorbid conditions such as diabetes and osteoarthritis.
Abstract: e20505 Background: Neuropathic pain (NP) remains difficult to control for a significant proportion of patients with cancer. Chemotherapy induced peripheral neuropathy (CIPN) is postulated as an ini...
49 citations
TL;DR: Although there are still great challenges associated with preventing and treating pain and altered sensations due to CIPN, there are preventative strategies and therapeutic options that can certainly improve the quality of life of patients who have cancer.
48 citations
01 Jan 2009
TL;DR: The ped‐mTNS is a feasible measure of CIPN and further research is warranted, and impairments were found in pin sensibility, vibration, distal muscle strength, and deep tendon reflexes.
Abstract: &NA; The aim of this study was to develop and test the feasibility of a chemotherapy‐induced peripheral neuropathy (CIPN) measurement, the ped‐mTNS, for use in school‐aged children. After adapting an established adult measure (modified‐Total Neuropathy Scale), the ped‐mTNS was administered one time to 20 children ages 5 ‐ 18 who were undergoing, or had recently completed, chemotherapy. The ability to complete the measurements, to be understood by school‐aged children and represent their symptoms, and the frequency of signs and symptoms was assessed. The ped‐mTNS was successfully completed in all children in under 10 minutes. Three children reported symptoms not covered by test items. Sixty percent (12/20) reported sensory symptoms and 55% (11/20) reported motor symptoms. On clinical examination, impairments were found in pin sensibility (30%), vibration (50%), distal muscle strength (90%), and deep tendon reflexes (95%). The mean score was 6.1 ± 3.8 out of possible 24. The ped‐mTNS is a feasible measure of CIPN and further research is warranted.
30 citations
TL;DR: Novel aspects of the IMiDs compounds, including substantial increase in potency and an interesting tolerability profile, primarily due to a decreased incidence of the most severe side effect of thalidomide, are discussed.
Abstract: IMiDs compounds are a class of analogues of thalidomide, with greater immunomodulatory activity and a superior safety profile compared to the parent compound. They show substantial increase in potency and an interesting tolerability profile, primarily due to a decreased incidence of the most severe side effect of thalidomide, i.e. Chemotherapy-Induced Peripheral Neurotoxicity (CIPN). These novel aspects of the IMiDs compounds will be discussed.
27 citations
TL;DR: Cavaletti et al. as mentioned in this paper developed the CI-PERINOMS (Chemotherapy Induced-Peripheral Neuropathy Outcome Measures Study protocol) to assess and monitor CIPN.
Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a major and potentially dose-limiting adverse event of several chemotherapeutic agents (Windebank and Grisold, 2008). CIPN is characterized by distal symmetrical numbness, tingling, paresthesias, dysesthesias, pain and/or weakness, which significantly affect functionality and quality of life (Aaronson, 1998). The incidence of CIPN may be as high as 100% in treated patients, depending on dose and dose-intensity of the chemotherapeutic regimen. The neurotoxic side effects may be permanent, and treatment is usually difficult. Neuroprotective agents that would either prevent or ameliorate CIPN are currently under investigation (Cavaletti and Marmiroli, 2006; Albers et al., 2007). However, before studying these agents in clinical trials, it is crucial to be able to assess CIPN in a simple, valid, and reproducible way in accordance with postulated international guidelines (Hobart et al., 1996; Merkies and Lauria, 2006). Although several scales have been used by oncologists and neurologists, grading CIPN is still an unsolved issue (Postma and Heimans, 2000; Cavaletti et al., 2007). Moreover, most of the scales have not undergone rigorous clinimetric evaluation and analysis, which are nowadays essential requirements for any proposed clinical trial (van Nes et al., 2008). The CI-PERINOMS: Chemotherapy Induced-Peripheral Neuropathy Outcome Measures Study protocol was developed by experienced neurologists to identify the best method(s) to assess and monitor CIPN (Cavaletti, 2008). After a consensus meeting held in Pomezia (Italy, June 22, 2007) where the CI-PERINOMS protocol was developed, and after local Institutional Review Board (IRB) approval, neurologists and oncologists from 21 centers in the United States and the European Union, selected based on their capability to perform the comprehensive testing and to recruit the types of subjects appropriate for this study, are now assessing the validity and reproducibility of the selected outcome measures. The primary endpoint of the study is to determine the validity and reproducibility of the proposed outcome measures in CIPN. Secondary objectives are the development of an overall disability sum-score (ODSS) specific to CIPN and the development of a responsiveness study based on the results of the study. According to the protocol, the clinimetric assessment of CIPN will be performed at two levels: a Core and an Extended study. The Core study has been designed to be feasible in both Oncology and Neurology departments, whereas the Extended study requires a neurophysiological examination. As part of the Core study, all the subjects will be examined with the following scales: TNSc = Total Neuropathy Score, clinical version (Cornblath et al., 1999; Cavaletti et al., 2003; 2006); VAS = visual analog pain scale (Maxwell, 1978); PI-NRS = 11-point-pain intensity numerical scale (Farrar et al., 2001); C-ODSS = calibrated-overall disability sumscore (Merkies et al., 2002); NCI-CTC 3.0 = National Cancer Institute-Common Toxicity Criteria, version 3.0; QLQ-CIPN20 EORTC = quality of life questionnaire for CIPN and QLQ-C30 = EORTC 30item questionnaire for cancer patients (Postma et al., 2005); QoL-PS = quality of life personal score. The Extended study, performed in a subgroup of patients, will consist of the Core measures plus Sensory examination by modified INCAT sensory sumscore (mISS) and nerve conduction studies. For the assessment of inter-observer and intraobserver and test–retest studies, two investigators in each participating center will evaluate study subjects, applying the selected impairment and activity limitation scales. Electrophysiological studies will be performed only once at entry. Subjects will be examined at two different occasions at the outpatient clinics. During the first visit, the two examiners will perform their scores independently and consecutively within 2 hours (interobserver measures). Within 1–3 weeks, the subject will return for a second visit and both investigators will re-examine the subject (intra-observer values) without having access to previous results. The outcome
27 citations
TL;DR: ALCAR does not affect the cytotoxicity of paclitaxel or carboplatin and there was no increase in proliferation, or NGFR of OVCAR-3 or SKOV-3 cells exposed to ALCAR.
TL;DR: Topical treatment with BAK-PLO appears to moderately improve symptoms of CIPN, and this topical gel was well tolerated without systemic side effects.
Abstract: 9531 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a prevalent dose limiting toxicity for several important cancer treatment agents. CIPN can impair function and cause distress. There are no proven pharmacologic treatments for established CIPN currently. This double blind randomized placebo controlled trial evaluated a compounded topical gel for this problem. The novelty of this treatment is that it might incorporate several agents with different mechanisms of action to provide relief locally without negative systemic effects. Methods: Patients with CIPN (rated ≥4 out of 10) for at least one month, related to previous and/or concurrent exposure to neurotoxic agents, were randomized to baclofen 10 mg, amitriptyline HCL 40 mg and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) vs placebo (PLO) to determine its effect on numbness, tingling, pain, and motor function. Exclusion criteria included other causes and/or current treatment for peripheral neuropathy. The primary endpoint w...
TL;DR: Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy but it appeared to be well tolerated.
Abstract: 9532 Background: Chemotherapy induced peripheral neuropathy (CIPN) continues to be a substantial problem for many cancer patients (pts). Pursuant to promising appearing pilot data, the current study evaluated the use of vitamin E for the prevention of CIPN. Methods: A phase III, randomized, double-blind, placebo controlled study was conducted in pts undergoing therapy with neurotoxic chemotherapy, utilizing twice daily dosing of vitamin E (400mg)/placebo. The primary endpoint was the incidence of grade 2+ sensory neuropathy (SN) toxicity (CTCAE v 3.0) in each treatment arm, analyzed by Chi-square testing. Major eligibility criteria included: planned curative intent adjuvant chemotherapy with neurotoxic chemotherapy, ≥ 18 years of age, ECOG PS of ≤2, no existing peripheral neuropathy or coronary artery disease, no prior treatment with neurotoxic chemotherapy, and no concurrent treatment with neuropathic or opioid pain medication. Planned sample size was 100 patients per arm, to provide 80% power to detect ...
TL;DR: The most common moderate to severe CIPN symptoms were numbness and tingling with shooting/burning pain being less common and the CTC neuropathy grading scale appears to be less sensitive than the CIPn20 in picking up sensory symptoms.
Abstract: 9587 Background: CIPN is characterized by adjectives not covered directly by most common measures of pain and functional limitations. Possible descriptors include numbness, tingling and shooting/burning pain. A prospective neuropathy treatment trial provided data to explore the relationship between self-reported aspects of this symptom. Methods: Baseline EORTC QLQ CIPN20 data and NCI CTCAE V3.0 (CTC)neuropathy grade (I-IV) were provided for all patients on trial. Spearman correlation coefficients and Kappa's coefficients of agreement were calculated between individual items and subscales of the CIPN20 as well as the CTC neuropathy scale. Simple regression models were applied to examine the association between the sensory symptoms and motor function in the fingers/hands (F/H). 200 patients provided 80% power to detect a correlation coefficient of 0.20 with a 5% Type I error. Results: A majority of patients reported “quite a bit” to “very much” numbness (57%) or tingling (62%) in F/H compared to “a little” ...
TL;DR: Treatment with CBs appears to benefit some patients with CIPN, and improvement in pain improved in 7/8 pts with CB treatment, which is as much as 7 points on an 11 point VAS.
Abstract: e20743 Background: CIPN is a common toxicity associated with the use of chemotherapy (CT) agents such as platinums, taxanes and vinca alkaloids. Patients (pts) may suffer from pain that adversely a...
01 Jan 2009
Dissertation•
01 Aug 2009
TL;DR: In the first part of the project, the temperature perceptional changes in terms of brain activation patterns of the chemotherapy patients with CIPN are studied using brain function MRI and the developed temperature fMRI protocol shows good reliability in detecting temperature response.
Abstract: Chemotherapy Induced Peripheral Neuropathy (CIPN) is known to im pact negatively on patients' quality of life. It has been reported that these patients tend to have sensitivity thresholds to stimuli, such as pain and tem perature, that are different from those of normal subjects. The effect of chemotherapeutic agents on the central nervous system (CNS) has been ob served; however, most of the mechanisms involved are not exactly understood. A quantitative investigation into the temperature sensitivity changes in the spinal cords and brains of chemotherapy patients would provide important information in understanding the side effects of this treatment modality. In the first part of the project, the temperature perceptional changes in terms of brain activation patterns of the chemotherapy patients with CIPN are studied using brain function MRI. In the second part of the project, the structural changes of the brain and spinal cord of chemotherapy patients with CIPN are studied using diffusion tensor imaging (DTI). High b-value (b = 1500 s/mm ) and low b-value (b=650 s/mm2 ) settings will be use during the spinal cord DTI scans. Due to the sample size limitation, no comparison between healthy vol unteers and CIPN patients can be done based on the existing temperature fMRI data. However, the developed temperature fMRI protocol shows good reliability in detecting temperature response. Based on the spinal cord DTI result using b = 1500 s/mm , decrease in FA value has been observed. The corresponding FA values of CIPN patient and healthy volunteers are 0.28±0.10 and 0.41±0.02 , respectively. ( t-test = 2.63 >2.447, p=0.05 level of signifi