scholarly journals Emerging Pharmacological and Non-Pharmacological Therapeutics for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 766
Author(s):  
Yang Li ◽  
Maryam B. Lustberg ◽  
Shuiying Hu
Keyword(s):  
Peripheral Neuropathy ◽  
Chemotherapeutic Agents ◽  
Common Adverse Event ◽  
Platinum Compounds ◽  
First Line ◽  
Effective Strategies ◽  
Effective Interventions ◽  
Prevention And Treatment ◽  
Mechanistic Understanding

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of several first-line chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib, which negatively affects the quality of life and clinical outcome. Given the dearth of effective established agents for preventing or treating CIPN, and the increasing number of cancer survivors, there is an urgent need for the identification and development of new, effective intervention strategies that can prevent or mitigate this debilitating side effect. Prior failures in the development of effective interventions have been due, at least in part, to a lack of mechanistic understanding of CIPN and problems in translating this mechanistic understanding into testable hypotheses in rationally-designed clinical trials. Recent progress has been made, however, in the pathogenesis of CIPN and has provided new targets and pathways for the development of emerging therapeutics that can be explored clinically to improve the management of this debilitating toxicity. This review focuses on the emerging therapeutics for the prevention and treatment of CIPN, including pharmacological and non-pharmacological strategies, and calls for fostering collaboration between basic and clinical researchers to improve the development of effective strategies.

scholarly journals Peripheral Neuropathy and Pain Caused by Cancer Chemotherapy

2021 ◽  
Vol 39 (1) ◽  
pp. 1-9
Author(s):  
Kyomin Choi ◽  
Jeeyoung Oh
Keyword(s):  
Quality Of Life ◽  
Peripheral Neuropathy ◽  
Clinical Characteristics ◽  
Proteasome Inhibitors ◽  
Chemotherapeutic Agents ◽  
Vinca Alkaloids ◽  
Platinum Compounds ◽  
Medical Environment ◽  
Preventive Methods

Peripheral neuropathy and pain are common adverse effects of chemotherapy, which incidence are rising significantly commensurate with extension of survival period in cancer patients. Chemotherapy-induced peripheral neuropathy is caused by most commonly used chemotherapeutic agents including platinum compounds, taxenes, proteasome inhibitors, thalidomide, and vinca alkaloids. Management of neuropathy and pain caused by chemotherapy is still challenging due to there is no proven therapies and preventive methods. The pain and its impact are becoming a main deterioration factor in quality of life and economic burden in our society. We review the mechanism, clinical characteristics, updated evidence of possible management of neuropathy and pain caused by traditional chemotherapeutic agents for contributing to the application of clinicians in their actual medical environment.

scholarly journals Application Potential of Plant-Derived Medicines in Prevention and Treatment of Platinum-Induced Peripheral Neurotoxicity

2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaowei Xu ◽  
Liqun Jia ◽  
Xiaoran Ma ◽  
Huayao Li ◽  
Changgang Sun
Keyword(s):  
Clinical Trials ◽  
Plant Secondary Metabolites ◽  
Chemotherapeutic Agents ◽  
Common Adverse Event ◽  
Sufficient Evidence ◽  
Peripheral Neurotoxicity ◽  
Herbal Products ◽  
Prevention And Treatment ◽  
Platinum Agents

As observed with other chemotherapeutic agents, the clinical application of platinum agents is a double-edged sword. Platinum-induced peripheral neuropathy (PIPN) is a common adverse event that negatively affects clinical outcomes and patients’ quality of life. Considering the unavailability of effective established agents for preventing or treating PIPN and the increasing population of cancer survivors, the identification and development of novel, effective interventions are the need of the hour. Plant-derived medicines, recognized as ideal agents, can not only help improve PIPN without affecting chemotherapy efficacy, but may also produce synergy. In this review, we present a brief summary of the mechanisms of platinum agents and PIPN and then focus on exploring the preventive or curative effects and underlying mechanisms of plant-derived medicines, which have been evaluated under platinum-induced neurotoxicity conditions. We identified 11 plant extracts as well as 17 plant secondary metabolites, and four polyherbal preparations. Their effects against PIPN are focused on oxidative stress and mitochondrial dysfunction, glial activation and inflammation response, and ion channel dysfunction. Also, ten clinical trials have assessed the effect of herbal products in patients with PIPN. The understanding of the molecular mechanism is still limited, the quality of clinical trials need to be further improved, and in terms of their efficacy, safety, and cost effectiveness studies have not provided sufficient evidence to establish a standard practice. But plant-derived medicines have been found to be invaluable sources for the development of natural agents with beneficial effects in the prevention and treatment of PIPN.

scholarly journals Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Muh. Akbar Bahar ◽  
Tsugunobu Andoh ◽  
Keisuke Ogura ◽  
Yoshihiro Hayakawa ◽  
Ikuo Saiki ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Herbal Medicine ◽  
Tumor Growth ◽  
Mechanical Allodynia ◽  
Chemotherapeutic Agents ◽  
Antitumor Action ◽  
Effective Strategies ◽  
Anti Cancer ◽  
Mammary Fat Pad ◽  
4T1 Cells

Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation) inhibited the tumor growth, and Goshajinkigan (1 g/kg, oral, daily from day 2 postinoculation) did not affect the antitumor action of paclitaxel. Mechanical allodynia developed in the inoculated region due to tumor growth and in the hind paw due to paclitaxel-induced neuropathy. Paclitaxel-induced allodynia was markedly prevented by Goshajinkigan, although tumor-associated allodynia was not inhibited by Goshajinkigan. These results suggest that Goshajinkigan prevents paclitaxel-induced peripheral neuropathy without interfering with the anti-cancer action of paclitaxel.

Pilot study of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9075-9075 ◽  
Author(s):  
Deirdre R. Pachman ◽  
Breanna M. Linquist ◽  
Debra L. Barton ◽  
Kelliann C. Fee-Schroeder ◽  
Thomas J. Smith ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Pilot Trial ◽  
Chemotherapeutic Agents ◽  
Controlled Clinical Trial ◽  
Effective Interventions ◽  
Days Of Therapy ◽  
Patient Reported ◽  
History Of ◽  
Scrambler Therapy ◽  
Ecog Ps

9075 Background: Chemotherapy-induced peripheral neuropathy (CIPN), a common dose-limiting side effect of chemotherapy, remains without known effective interventions. Preliminary data support that Scrambler therapy, a device which treats pain via non-invasive cutaneous electrostimulation, is beneficial for the treatment of CIPN. This pilot trial was performed to investigate the effect of Scrambler therapy for the treatment of CIPN. Methods: Eligible patients included those age ≥18 years, ECOG PS ≤2, life expectancy ≥3 months, with pain or CIPN symptoms of ≥1 month duration and tingling or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area for up to 10 daily 30 minute sessions. Symptoms were monitored daily during therapy using a questionnaire to measure symptoms of neuropathy with a numerical analogue scale. Results: We report on the first 11 CIPN patients, enrolled between 7/18/2011 and 12/12/2011, 3 men and 8 women; mean age 57 years. Patients had history of exposure to various chemotherapeutic agents and the majority had symptoms >2 years. The table portrays data at baseline, at the end of the 10 planned days of therapy, and the percent changes from baseline to the end of treatment, regarding patient reported pain, tingling, and numbness over the preceding 24 hours. There were no adverse events. Persistent benefit out to 5 weeks was seen in some patients; maturing data will be available by May 2012. Descriptive summary statistics formed the basis of data analysis. Further patients are being entered on this trial. Conclusions: Scrambler therapy appears to be beneficial in the treatment of CIPN. A prospective placebo-controlled clinical trial should be performed to confirm these preliminary findings. [Table: see text]

scholarly journals Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy

2021 ◽  
Vol 22 (17) ◽  
pp. 9257
Author(s):  
Chih-Hung Tsai ◽  
Yuan-Ho Lin ◽  
Yung-Sheng Li ◽  
Trung-Loc Ho ◽  
Le Huynh Hoai Thuong ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Recent Progress ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Common Side Effect ◽  
Integrated Medicine ◽  
Effective Prevention ◽  
Effective Strategies ◽  
Prevention And Treatment

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

An Overview of Chemotherapy-Induced Peripheral Neuropathy

2008 ◽  
Vol 21 (2) ◽  
pp. 138-145 ◽  
Author(s):  
Jose R. Murillo ◽  
James E. Cox ◽  
Michael S. Oholendt
Keyword(s):  
Adverse Event ◽  
Peripheral Neuropathy ◽  
Positive Impact ◽  
Chemotherapeutic Agents ◽  
Patient Specific ◽  
Drug Discontinuation ◽  
Neurologic Complication ◽  
Patients With Cancer ◽  
Neurological Adverse Event

Peripheral neuropathy remains a major limitation of chemotherapeutic agents used in cancer treatment. This neurologic complication from chemotherapy occurs frequently and can be debilitating. Although difficult to predict, both chemotherapeutic and patient-specific risk factors may contribute to this adverse event. Symptoms of peripheral neuropathy may appear acutely after treatment or persist chronically upon drug discontinuation. The taxanes, vinca alkaloids, and immunomodulatory drugs commonly cause peripheral nervous system toxicity. Prompt recognition and evaluation of this neurological adverse event by those who provide care to patients with cancer can prove to have a positive impact on the quality of life of those patients.

scholarly journals The Role of Nucleotide Excision Repair in Cisplatin-Induced Peripheral Neuropathy: Mechanism, Prevention, and Treatment

2021 ◽  
Vol 22 (4) ◽  
pp. 1975
Author(s):  
Scarlett Acklin ◽  
Fen Xia
Keyword(s):  
Peripheral Neuropathy ◽  
Nucleotide Excision Repair ◽  
Excision Repair ◽  
Life Saving ◽  
Platinum Based Chemotherapy ◽  
Nucleotide Excision ◽  
Prevention And Treatment ◽  
Integral Role

Platinum-based chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting effects of cancer treatment and results in dose reduction and discontinuation of life-saving chemotherapy. Its debilitating effects are often permanent and lead to lifelong impairment of quality of life in cancer patients. While the mechanisms underlying the toxicity are not yet fully defined, dorsal root ganglia sensory neurons play an integral role in symptom development. DNA-platinum adducts accumulate in these cells and inhibit normal cellular function. Nucleotide excision repair (NER) is integral to the repair of platinum adducts, and proteins involved in its mechanism serve as potential targets for future therapeutics. This review aims to highlight NER’s role in cisplatin-induced peripheral neuropathy, summarize current clinical approaches to the toxicity, and discuss future perspectives for the prevention and treatment of CIPN.

scholarly journals MORPHOLOGICAL MANIFESTATIONS OF EXPERIMENTAL PACLITAXEL-INDUCED SICK NERVE NEUROPATHY UNDER CORRECTION OF 2-ETHYL-6-METHYLIDE-3-HYCYDYR-3-HYDYCIDE-3

2021 ◽  
Vol 2 (4(68)) ◽  
pp. 32-38
Author(s):  
M. Ostrovskij ◽  
S. Gerashenko
Keyword(s):  
Peripheral Neuropathy ◽  
Isotonic Saline ◽  
Therapeutic Tool ◽  
Morphological Studies ◽  
White Rats ◽  
Prevention And Treatment ◽  
Pharmacological Potential ◽  
Sedative Action ◽  
Effective Drugs

Paclitaxel is an effective chemotherapeutic agent for many cancers, but has a number of limiting side effects that not only significantly reduce the quality of life of patients, but also limit their further treatment. Peripheral neuropathy is one of these, but as of today, there are no proven effective drugs for the prevention or treatment of paclitaxel-induced neuropathic pain (IDP) in particular, or peripheral chemotherapy-induced neuropathy (PIH) in general. 2-ethyl-6-methyl-3-hydroxypyridine succinate (HS) is a derivative of succinic acid with neuroprotective, antihypoxic, membrane-protective, nootropic, sedative action. The experiment was performed on 80 white rats injected intraperitoneally with paclitaxel (Actavis, Romania), pre-dissolved in isotonic saline at a dose of 2 mg / kg body weight four times a day until a total dose of 8 mg / kg. Forty of these animals were then injected intraperitoneally with 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (the other 40 rats received intraperitoneal water for injection). Morphological studies were performed on the 1st, 7th, 15th, 28th, 60th, 90th and 120th days after the last administration of the drug. We investigated the pharmacological potential of HS in the prevention and treatment of PNH at the level of the sciatic nerve (CH). Our results allow us to conclude that the introduction of HS creates a protective effect against paclitaxel-induced peripheral neuropathy (PIPN) by affecting both the axial cylinder and the myelin sheath of HF. Due to the known pathophysiological mechanisms of neuropathy, this method can be a promising therapeutic tool for the prevention and treatment of PIPN.

scholarly journals Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Giulia Fumagalli ◽  
Laura Monza ◽  
Guido Cavaletti ◽  
Roberta Rigolio ◽  
Cristina Meregalli
Keyword(s):  
Peripheral Neuropathy ◽  
Proteasome Inhibitors ◽  
Chemotherapeutic Agents ◽  
Peripheral Neuropathies ◽  
Drg Neurons ◽  
Toxic Agent ◽  
Cytokines And Chemokines ◽  
Secretion Of Mediators ◽  
Blood Brain Barrier Integrity

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.

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

2019 ◽  
Vol 48 (1) ◽  
pp. 190-201 ◽  
Author(s):  
Sandy Eldridge ◽  
Liang Guo ◽  
John Hamre
Keyword(s):  
Peripheral Neuropathy ◽  
Anticancer Agents ◽  
Clinical Presentation ◽  
In Vitro Models ◽  
Comparative Review ◽  
Prevention And Treatment ◽  
Underlying Mechanisms

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.

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