scholarly journals Chemotherapy-induced peripheral neuropathy: an update on the current understanding

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1466 ◽  
Author(s):  
James Addington ◽  
Miriam Freimer

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

2015 ◽  
Vol 308 (4) ◽  
pp. G223-G232 ◽  
Author(s):  
Vanesa Stojanovska ◽  
Samy Sakkal ◽  
Kulmira Nurgali

The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.


Author(s):  
Radhey Shyam ◽  
Arpita Singh ◽  
Dheeraj Kumar Singh ◽  
Ajay Kumar Verma ◽  
Pratap Shankar ◽  
...  

Background: In the modern era, AIDS is not less than a disaster for the human race. More than two-third of HIV-infected individuals have an associated infectious pulmonary disease. Mycobacterium tuberculosis is more virulent than most of other opportunistic pathogen causing latent infection. HIV is characterized by a profound immunodeficiency resulting from a progressive, quantitative and qualitative deficiency of the subset of CD4 T lymphocytes referred to as helper T cells leading to the patient at high risk of developing a variety of opportunistic infections. At present AIDS is incurable but some of the drugs have shown to decrease the mortality and morbidity of the disease. These are called as Highly Active Anti-Retroviral Therapy (HAART). However, these drugs are associated with a significant number of side effects. This work has been conducted in order to study the demographic profile of HIV patients with TB and monitor the adverse effects of different HAART regimens among them.Methods: A total of 3078 patients screened for the study. Those who were diagnosed with HIV were enrolled. Pretreatment parameters like, CD4, CD8 + lymphocyte count and their ratio, haemogram etc. were recorded. Patients were divided into four groups and were started with different HAART regimens. They were monitored regularly for the appearance of any adverse effects.Results: The prevalence of HIV sero-positivity was found to be 3.60%. Out of them, 71.18% were males and 28.82% were females. The highest prevalence (43.29%) was in the age group of 21-50 years. The sero-positive rate was found more in married males as compared to married females and unmarried cases. Side effects were present in all the groups. The most common side effect was GI intolerance and was most frequent in Group I. Anemia and neutropenia occurred in the Zidovudine containing groups (group I, III and IV). Peripheral neuropathy occurred most commonly in cases of Group II. Rashes occurred in nevirapine containing groups. Liver function derangement was noticed more in group I and II. 71.4% of patients on HAART regimen showed improvement in symptoms while 28.57% did not show any improvement.Conclusions: The prevalence of HIV sero-positivity in our study was 3.60%. The rate of sero-positivity was more in males as compared to females while it was highest in the individuals of 21-50 years of age. The most common side effect was GI intolerance and was most frequent in Group I. Anemia and neutropenia occurred most frequently in Zidovudine containing groups. Peripheral neuropathy occurred most commonly in cases of Group II (Stavudine + Lamivudine + Nevirapine). Deranged lipid profile was found to occur due to indinavir in patients of Group IV. After starting on HAART regimens, 74.4% showed significant improvement in symptoms.


Phlebologie ◽  
2004 ◽  
Vol 33 (06) ◽  
pp. 202-205 ◽  
Author(s):  
K. Hartmann ◽  
S. Nagel ◽  
T. Erichsen ◽  
E. Rabe ◽  
K. H. Grips ◽  
...  

SummaryHydroxyurea (HU) is usually a well tolerated antineoplastic agent and is commonly used in the treatment of chronic myeloproliferative diseases. Dermatological side effects are frequently seen in patients receiving longterm HU therapy. Cutaneous ulcers have been reported occasionally.We report on four patients with cutaneous ulcers whilst on long-term hydroxyurea therapy for myeloproliferative diseases. In all patients we were able to reduce the dose, or stop HU altogether and their ulcers markedly improved. Our observations suggest that cutaneous ulcers should be considered as possible side effect of long-term HU therapy and healing of the ulcers can be achieved not only by cessation of the HU treatment, but also by reducing the dose of hydroxyurea for a limited time.


2020 ◽  
Vol 21 (3) ◽  
pp. 288-301 ◽  
Author(s):  
Lin Zhou ◽  
Luyao Ao ◽  
Yunyi Yan ◽  
Wanting Li ◽  
Anqi Ye ◽  
...  

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.


2020 ◽  
pp. 107815522097062
Author(s):  
Uğur Çelik ◽  
Ertuğrul H Aydemir ◽  
Burhan Engin ◽  
Muazzez Ç Oba ◽  
Mesut Yılmaz ◽  
...  

Introduction Novel anti-cancer drugs such as targeted cancer therapies and immune check-point inhibitors (ICIs) have adverse events, especially concerning the skin. The aim of this study is to report an overview of the commonly consulted dermatological side effects of ICIs and targeted cancer therapies in clinical practice, along with their management. Methods In this single-center study, we evaluated consecutive oncological patients who were referred from the oncology outpatient clinic to the dermatology outpatient clinic due to skin side effects of ICIs and targeted therapies. All patients were examined and treated at the same day of referral by experienced dermatologists. Patient characteristics, clinical findings, diagnostic workups and treatments were retrieved from outpatient records. Results Sixty three patients were enrolled. Most common diagnoses were lung carcinoma, melanoma and colon carcinoma. Fifty patients (79%) were using targeted therapies while 13 (21%) were using ICIs. Xerosis was the most common side effect (44%), followed by acneiform rash, paronychia, eczema and pruritus. Majority of the side effects were grade 2 and 3. Psoriasis was a common side effect of ICIs. One patient had a newly developed dysplastic nevus on vemurafenib treatment. Oncological treatment was not withheld in any of the patients. Conclusions This study revealed the most commonly consulted skin side effects of novel anti-cancer drugs and their management in daily practice. We underlie the importance of collaborative work of oncology and dermatology professionals as early management of cutaneous side effects of targeted therapies and ICIs improves patient outcomes.


2020 ◽  
pp. bjophthalmol-2020-316970 ◽  
Author(s):  
Blake Hugo Fortes ◽  
Harris Liou ◽  
Lauren A Dalvin

Background/AimsTo investigate immune-related ophthalmic side effects of systemic checkpoint inhibitors and compare side effect frequency and requirement for cessation of immunotherapy by checkpoint target.MethodsPatients taking immune checkpoint inhibitors at a single centre from January 1, 2010 to February 29, 2020 were retrospectively reviewed for clinical characteristics, treatments and concurrent systemic adverse effects.ResultsOf 996 patients, 28 (2.8%) experienced an ophthalmic side effect that came to the attention of an eye care provider. Mean age at presentation of the side effect was 63 years (median 64, range 25–88). The checkpoint inhibitor most often preceding side effects was pembrolizumab in 12 (43%). The most common side effect was dry eye in 16 (57%), followed by uveitis in 4 (14%) patients, and singular cases of ptosis and binocular diplopia, among others. Ocular surface adverse effects occurred more frequently with programmed death ligand-1 (PD-L1) targeting therapy. There were no significant differences in the frequency of orbit/ocular adnexa and uveitis or retinal side effects based on checkpoint targets. Follow-up was available in 13 (46%) patients, with mean duration of 20 months (median 16, range 2–52 months). Of these patients, the ophthalmic side effects were controlled without discontinuing therapy in 12 (92%). Checkpoint inhibitor cessation was required in one patient with panuveitis.ConclusionOphthalmic immune-related adverse events are rare but could be more common than previously estimated. PD-L1-directed checkpoint inhibitors may have a slight predilection for ocular surface adverse effects. Most ophthalmic events can be treated with targeted therapy without discontinuation of life-prolonging immunotherapy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24080-e24080
Author(s):  
Eva Battaglini ◽  
David Goldstein ◽  
Susanna Park

e24080 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major yet poorly understood side effect of cancer treatment, leading to symptoms including numbness, tingling and pain. It can lead to cessation of effective treatment, long-term functional disability and reduced quality of life. Despite this, there is currently little understanding of its impact. Methods: The aim of the study was to investigate the impact of neurotoxic chemotherapy side effects on the lives of cancer survivors. Data was collected via an online survey covering demographics, cancer diagnosis and treatment, CIPN and other side effects of chemotherapy, using standardised measures to assess comorbidities, quality of life, physical activity, pain and CIPN symptoms. Results: Data was analysed from 986 respondents who were treated with neurotoxic therapies (83% female, 16% male), with mean age 59 years ( SD 10.7 years). A majority of respondents were treated for breast cancer (59%), 14% for colorectal cancer and 11% for multiple myeloma. Chemotherapy types received included paclitaxel (32%), docetaxel (32%) and oxaliplatin (13%), and respondents completed treatment a mean of 3.6 years ago. The majority of respondents (80%) reported experiencing neuropathic symptoms after finishing chemotherapy, with 77% reporting current CIPN. Those with CIPN reported functional impacts, with 23% reporting moderate to severe problems with hand function and 28% reporting moderate to severe walking difficulties. CIPN was second most commonly rated as the treatment side effect having the greatest impact, following fatigue. Respondents with high levels of current CIPN symptoms had poorer quality of life, more comorbid health conditions, higher BMI and more often received multiple neurotoxic chemotherapies than those with low levels of CIPN symptoms. In addition, respondents who reported meeting government physical activity guidelines had lower CIPN and higher quality of life scores than those who did not meet the guidelines. Regression analyses investigating the association between quality of life and clinical and sociodemographic characteristics resulted in a model with comorbid health conditions, CIPN symptoms, years since treatment, age and physical activity as significant predictors of quality of life. Conclusions: These findings suggest that CIPN has a lasting impact on cancer survivors, leading to decreases in quality of life, often occurring alongside poorer general health. This impact supports the need for further research to improve assessment, prevention and treatment.


2015 ◽  
Vol 38 (3) ◽  
pp. E14 ◽  
Author(s):  
Azeem A. Rehman ◽  
Kevin B. Elmore ◽  
Tobias A. Mattei

Glioblastoma is both the most common and most lethal primary CNS malignancy in adults, accounting for 45.6% of all malignant CNS tumors, with a 5-year survival rate of only 5.0%, despite the utilization of multimodal therapy including resection, chemotherapy, and radiation. Currently available treatment options for glioblastoma often remain limited, offering brief periods of improved survival, but with substantial side effects. As such, improvements in current treatment strategies or, more likely, the implementation of novel strategies altogether are warranted. In this topic review, the authors provide a comprehensive review on the potential of alternating electric fields (AEFs) in the treatment of glioblastoma. Alternating electric fields—also known as tumor-treating fields (TTFs)—represent an entirely original therapeutic modality with preliminary studies suggesting comparable, and at times improved, efficacy to standard chemotherapeutic agents in the treatment of recurrent glioblastoma. A recent multicenter, Phase III, randomized clinical trial comparing NovoTTF-100A monotherapy to physician's best choice chemotherapy in patients with recurrent glioblastoma revealed that AEFs have similar efficacy to standard chemotherapeutic agents with a more favorable side-effects profile and improved quality of life. In particular, AEFs were shown to have limited systemic adverse effects, with the most common side effect being contact dermatitis on the scalp at the sites of transducer placement. This study prompted FDA approval of the NovoTTF-100A system in April 2011 as a standalone therapy for treatment of recurrent glioblastoma refractory to surgical and radiation treatment. In addition to discussing the available clinical evidence regarding the utilization of AEFs in glioblastoma, this article provides essential information regarding the supposed therapeutic mechanism as well as modes of potential tumor resistance to such novel therapy, delineating future perspectives regarding basic science research on the issue.


2021 ◽  
Vol 2 ◽  
Author(s):  
Urszula O. Warncke ◽  
Wisam Toma ◽  
Julie A. Meade ◽  
Abigail J. Park ◽  
Danielle C. Thompson ◽  
...  

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose limiting, and long-lasting side effect of chemotherapy treatment. Unfortunately, no treatment has proven efficacious for this side effect. Rodent models play a crucial role in the discovery of new mechanisms underlying the initiation, progression, and recovery of CIPN and the potential discovery of new therapeutics. However, there is limited consistency in the dose, the sex, age, and genetic background of the animal used in these studies and the outcome measures used in evaluation of CIPN rely primarily on noxious and reflexive measures. The main objective of this study was to provide a comprehensive and systematic characterization of oxaliplatin-induced peripheral neuropathy in mice by using a battery of behavioral, sensory, electrophysiological, and morphometric measures in both sexes of the two widely used strains of mice, C57BL/6J and BALB/cJ. Mice received intraperitoneal injections of 3 or 30 mg/kg cumulative doses of oxaliplatin over the course of 2 weeks. Both doses induced long-term and time-dependent mechanical and cold hypersensitivity. Our results show that 30 mg/kg oxaliplatin reduced the locomotor activity in C57BL/6J mice, and C57BL/6J females showed anxiety-like behavior one-week post completion of treatment. In the same dose group, BALB/cJ males and females sustained a larger decrease in sucrose preference than either male or female C57BL/6J mice. Both strains failed to show significant changes in burrowing and nesting behaviors. Two clinically relevant assessments of changes to the peripheral nerve fibers, nerve conduction and intraepidermal nerve fiber density (IENFD) were evaluated. Only BALB/cJ females showed significant reduction in the nerve conduction amplitude 1 week after 30 mg/kg oxaliplatin regimen. Moreover, this dose of the chemo agent reduced the IENF density in both sexes and strains. Our findings suggest that mouse strain, sex, and assay type should be carefully considered when assessing the effects of oxaliplatin and potential therapeutic interventions.


2021 ◽  
Vol 14 (10) ◽  
pp. 1049
Author(s):  
Abanoub Riad ◽  
Andrea Pokorná ◽  
Jitka Klugarová ◽  
Natália Antalová ◽  
Lucia Kantorová ◽  
...  

Young adults had been widely perceived as a low-risk group for COVID-19 severity; therefore, they were deprioritised within the mass vaccination strategies as their prognosis of COVID-19 infection is relatively more favourable than older age groups. On the other hand, vaccination of this demographic group is indispensable to achieve herd immunity. A cross-sectional survey-based study was used to evaluate the side effects of mRNA-based COVID-19 vaccines among university students in the Czech Republic. The validated questionnaire was delivered in a digital form, and it consisted of demographic data; COVID-19 vaccine-related anamnesis; and local, systemic, orofacial, and skin-related side effects’ prevalence, onset, and duration. Out of the 539 included participants, 70.1% were females and 45.8% were <23 years old. The vast majority (95.2%) reported at least one side effect. The most common side effect was injection site pain (91.8%), followed by fatigue (62.5%), headache (36.4%), and muscle pain (34.9%). The majority of local side effects occurred after both doses (74.4%), while most systemic side effects occurred after the second dose only (56.2%). Most local (94.2%) and systemic (93.3%) side effects resolved within three days after vaccination. Females participants’ adjusted odds ratio (AOR) showed they were 2.566 (CI 95%: 1.103–5.970) times more likely to experience post-vaccination side effects, and the participants who received two doses reported an increased AOR of 1.896 (0.708–5.077) for experiencing side effects. The results of this study imply that mRNA-based COVID-19 vaccines are highly probably safe for young adults, and further studies are required to investigate the role of medical anamnesis, prior COVID-19 infection, and gender in side effects incidence.


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