taxane and Neuralgia

Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient's last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous cannabinoid system has shown great promise and efficacy in alleviating CIPN in preclinical and clinical studies. In this review, we will discuss the mechanisms through which the platinum, taxane, and vinca alkaloid classes of chemotherapeutics may produce CIPN and the potential therapeutic effect of drugs targeting the endocannabinoid system in preclinical and clinical studies, in addition to cannabinoid compounds diffuse mechanisms of action in alleviation of CIPN.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Cannabinoids; Chronic Pain; Clinical Trials as Topic; Humans; Neoplasms; Neuralgia; Organoplatinum Compounds; Taxoids; Treatment Outcome; Vinca Alkaloids

One in 2 Canadians is expected to acquire cancer in their lifetime. Many cancers, including breast, ovarian, and lung cancer, are treated using taxane chemotherapy with curative intent. A major adverse effect with the use of taxane chemotherapeutic agents is taxane-induced peripheral neuropathy (TIPN). Both positive (spontaneous pain, heightened sensitivity with light touch, tingling, itching, burning) and negative (loss of touch, loss of hot/cold sensations, and loss of pain) sensory symptoms can be experienced in the hands and feet and worsen with increasing dose and treatment duration. The pathophysiology of TIPN is still unknown but likely involves multiple mechanisms, including microtubule impairment, neuroimmune and inflammatory changes, ion channel remodeling, impaired mitochondrial function, and genetic predisposition. This review highlights current theories on the pathophysiology for TIPN, the cellular responses thought to maintain neuropathic pain, and the growing support for exercise in the treatment and prevention of peripheral neuropathy and neuropathic pain in both animal and human models.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Exercise Therapy; Humans; Neoplasms; Neuralgia; Peripheral Nervous System Diseases; Taxoids

In this review, we discuss the plight of Alice, a patient with advanced nonsmall cell lung cancer (NSCLC) who struggles with taxane-related peripheral neuropathy (PN). Using this unique point of view helps us to appreciate the implications of PN on daily activities as well as the difficulty in decision-making regarding continuation of treatment. In addition, published reports of phase 3 trials are reviewed to identify the incidence and severity of chemotherapy-induced PN as well as the assessment tools used in these studies.. A literature review spanning the years 1998-2012 was performed. Phase 3 studies and a meta-analysis of taxane-based therapy in advanced NSCLC were selected for review for their findings regarding the incidence and severity of chemotherapy-induced PN.. In total, 16 phase 3 studies and 1 meta-analysis were reviewed. Use of grading scales and PN assessment tools was inconsistent across the studies, and some studies did not report PN at all.. The true incidence and severity of chemotherapy-induced PN in clinical trials may be masked by nonstandardized reporting; thus, a more standardized approach to grading, assessing, and reporting PN in clinical trials is greatly needed to allow for appropriate comparisons across studies. Understanding chemotherapy-induced PN from the patient's perspective as well as the development of PN at the clinical trial level will help health care providers anticipate the development of PN and improve their ability to manage it.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Neuralgia; Peripheral Nervous System Diseases; Restless Legs Syndrome; Taxoids

Taxane-induced peripheral neuropathy (TIPN) is a main toxicity of taxanes with no effective treatment. This study aimed to compare the efficacy and safety of pregabalin (150 mg daily) and duloxetine (60 mg daily) for managing TIPN in breast cancer patients.. This randomized, double-blind, Phase II clinical trial was carried out at a chemotherapy center affiliated to Mazandaran University of Medical Sciences. Patients with breast cancer who received paclitaxel or docetaxel and had a grade 1 or more neuropathy (based on the National Cancer Institute Common Terminology Criteria for Adverse Events version (NCI-CTCAE v4.03), and who had score 4 or higher neuropathic pain severity [based on the visual analog scale (VAS)] were enrolled. Response to treatment was assessed based on improvements in the VAS, NCI-CTCAE, and Patient Neurotoxicity Questionnaire (PNQ) scores during a 6-week trial.. Both interventions were effective in decreasing TIPN compared to baseline. At Week 6, the VAS scores were improved in 37/40 (92.5%) and 16/42 (38.1%) of the patients in the pregabalin and duloxetine groups, respectively (p < 0.001). Improvement in NCI-CTCAE sensory neuropathy was also more significant with pregabalin (37/40; 92.5%) in comparison to duloxetine (13/42; 31%) (p < 0.001). Pregabalin was also more beneficial than duloxetine in improving the PNQ scores by 36/40 (90%) and 13/42 (31%), respectively (p < 0.001). Both interventions were tolerated well with mild adverse events.. Both pregabalin and duloxetine were well tolerated and efficacious in relieving neuropathic pain, however a 60 mg dose of duloxetine is inferior to a 150 mg dose of pregabalin.

Topics: Adult; Analgesics; Breast Neoplasms; Bridged-Ring Compounds; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Middle Aged; Neuralgia; Pregabalin; Surveys and Questionnaires; Taxoids; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Exercise Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Neuralgia; Neurological Rehabilitation; Outcome Assessment, Health Care; Peripheral Nervous System Diseases; Single-Blind Method; Taxoids

Neuropathic pain can be present in patients developing chemotherapy-induced peripheral neuropathy (CIPN). Nerve growth factor (NGF) is trophic to small sensory fibers and regulates nociception.. We investigated the changes in serum NGF and intraepidermal nerve fiber density in skin biopsies of cancer patients receiving neurotoxic chemotherapy in a single-center prospective observational study.. Patients were evaluated before and after chemotherapy administration. CIPN was graded with Total Neuropathy Score. Neuropathic pain was present in 13 of 60 patients (21%), who reported shooting or burning pain in the hands (n = 9) and the feet (n = 12). Patients displaying painful CIPN presented higher NGF after treatment compared with patients with painless or absent CIPN (8.7 ± 11.9 vs. 2.5 ± 1.4 pg/mL, P = 0.016). The change of NGF significantly correlated with neuropathic pain. Patients with painful CIPN did not show significant loss of IEFND compared with patients with painless or absent CIPN (6.16 ± 3.86 vs. 8.37 ± 4.82, P = 0.12). No correlation between IEFND and NGF was observed.. Serum NGF increases in cancer patients receiving taxane or platinum with painful CIPN, suggesting that it might be a potential biomarker of the presence and severity of neuropathic pain in this population. Long-term comprehensive studies to better define the course of NGF in relation with neurological outcomes would be helpful in the further design of therapies for CIPN-related neuropathic pain.

Topics: Antineoplastic Agents; Bridged-Ring Compounds; Female; Humans; Leg; Male; Middle Aged; Neoplasms; Nerve Growth Factor; Neural Conduction; Neuralgia; Pain Measurement; Platinum Compounds; Prospective Studies; Skin; Surveys and Questionnaires; Taxoids

To quantify the prevalence of neurological complications among breast cancer patients at one and three years after diagnosis, and to identify factors associated with neuropathic pain (NP) and chemotherapy-induced peripheral neuropathy (CIPN).. Prospective cohort study including 475 patients with newly diagnosed breast cancer, recruited among those proposed for surgical treatment (Portuguese Institute of Oncology, Porto). Patients underwent a neurological evaluation and had their cognitive function assesses with the Montreal Cognitive Assessment, before treatment and at one and three years after enrollment. We estimated the prevalence of each neurological complication, and odds ratios (OR), adjusted for socio-demographic and clinical characteristics, to identify factors associated with NP and CIPN.. More than half of the patients [54.7%, 95% confidence interval (95%CI): 50.2-59.2] presented at least one neurological complication, at one or at three years after cancer diagnosis. Between the first and the third year of follow-up, there was an increase in the prevalence of NP (from 21.1% to 23.6%), cognitive impairment (from 7.2% to 8.2%), cerebrovascular disease (from 0.6% to 1.5%) and brain metastasis (from 0.0% to 0.6%). The prevalence of CIPN decreased from 14.1% to 12.6%. Axillary lymph node dissection was associated with NP at one year (OR = 2.75, 95%CI: 1.34-5.63) and chemotherapy with NP at three years (OR = 2.10, 95%CI: 1.20-3.67). Taxane-based chemotherapy was strongly associated with prevalence of CIPN at one and three years.. Neurological complications are frequent even three years after cancer diagnosis and NP remained the major contributor to the burden of these conditions among survivors.

Topics: Adult; Antineoplastic Agents; Axilla; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Intraductal, Noninfiltrating; Cerebrovascular Disorders; Cognitive Dysfunction; Female; Follow-Up Studies; Humans; Lymph Node Excision; Middle Aged; Neuralgia; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Prevalence; Prospective Studies; Risk Factors; Survivors; Taxoids