To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors.
An Expert Panel ...conducted targeted systematic literature reviews to identify new studies.
The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update.
The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.
To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.
A systematic ...literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life.
A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.
On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity, negatively affecting both quality of life and disease outcomes. To date, there is no proven preventative ...strategy for CIPN. Although multiple randomized trials have evaluated a variety of pharmacologic interventions for the treatment of CIPN, only duloxetine has shown clear efficacy in a phase III study. The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee has identified CIPN as a priority for translational research in cancer care. Promising advances in preclinical research have identified several novel preventative and therapeutic targets, which have the potential to transform the care of patients with this debilitating neurotoxicity. Here, we provide an overarching view of emerging strategies and therapeutic targets that are currently being evaluated in CIPN.
Abstract
Aims
The national incidence, risk factors, and associated mortality of atrial fibrillation (AF) in breast cancer patients are unknown.
Methods and results
Using the Surveillance, ...Epidemiology, and End Results-Medicare-linked database, we identified females, ≥66 years old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrolees without cancer, and each pair was followed for 1 year to identify a primary outcome of AF. Cumulative incidence was calculated using competing risk survival statistics. Following this, identifying risk factors of AF among breast cancer patients was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan–Meier methods and adjusted Cox proportional hazards modelling were performed to estimate mortality in breast cancer patients with incident and prevalent AF. This study included 85 423 breast cancer patients. Among these 9425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New-onset AF was diagnosed in 2993 (3.9%) patients in a 1-year period after the breast cancer diagnosis incidence 3.3%, 95% confidence interval (CI) 3.0–3.5%, at 1 year; higher rate in the first 60 days (0.6%/month). Comparatively, the incidence of new-onset AF in matched non-cancer controls was 1.8% (95% CI 1.6–2.0%). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with the development of AF American Joint Committee on Cancer (AJCC) Stage II/III/IV vs. I: adjusted hazard ratio (aHR) 1.51/2.63/4.21, respectively. New-onset AF after breast cancer diagnosis (aHR 3.00) is associated with increased 1-year cardiovascular mortality.
Conclusion
AF incidence is significantly higher in women after a breast cancer diagnosis. Higher breast cancer stages at diagnos are significantly associated with a higher risk of AF. New-onset AF in the new breast cancer diagnosis setting increases 1-year cardiovascular mortality but not breast cancer-related mortality.
Key Question
What are the incidence, prevalence, risk factors and mortality outcomes of atrial fibrillation (AF) in a multi-ethnic representative United States cohort of breast cancer patients?
Key Finding
Annual incidence for AF is 3.9% with highest rate in the first 60 days after cancer diagnosis. Cancer stage and grade are the strongest risk factors for AF. New onset AF after breast cancer increases all-cause and cardiovascular mortality.
Take Home Message
AF incidence is higher in breast cancer patients and is associated with later stage and grade at diagnosis of breast cancer. Involving cardio-oncology in those who develop AF after cancer diagnosis should be encouraged to improve their cardiovascular and overall prognosis.
Graphical Abstract
Structured Graphical Abstract
Cumulative incidence function plot for atrial fibrillation in breast cancer patients compared with matched non-cancer patients. The start of follow-up is at breast cancer diagnosis or pseudo-diagnosis date for the non-cancer cohort. Partial forest plot showing risk factor analysis of atrial fibrillation after breast cancer diagnosis. Partial forest plot showing fully adjusted model for all-cause, cardiovascular, and breast cancer-specific mortality in those after new-onset atrial fibrillation after breast cancer diagnosis as well as those with atrial fibrillation prior to breast cancer diagnosis. AF, atrial fibrillation; HR, hazard ratios; ref, reference; AJCC, American Joint Committee on Cancer.
•Urgent need to better understand CICI pathobiology and develop treatment strategies.•Neuroinflammation and BBB damage present as likely mechanisms underlying CICI.•The microbiome has profound ...influence on CNS function.•Interactions between the microbiome and CNS may regulate neurotoxicity development.•Pre-chemotherapy microbial composition could predict CICI risk.
Chemotherapy-induced cognitive impairment (CICI) is an ill-defined complication of chemotherapy treatment that places a significant psychosocial burden on survivors of cancer and has a considerable impact on the activities of daily living. CICI pathophysiology has not been clearly defined, with candidate mechanisms relating to both the direct cytotoxicity of chemotherapy drugs on the central nervous system (CNS) and more global, indirect mechanisms such as neuroinflammation and blood brain barrier (BBB) damage. A growing body of research demonstrates that changes to the composition of the gastrointestinal microbiota is an initiating factor in numerous neurocognitive conditions, profoundly influencing both CNS immunity and BBB integrity. Importantly, chemotherapy causes significant disruption to the gastrointestinal microbiota. While microbial disruption is a well-established factor in the development of chemotherapy-induced gastrointestinal toxicities (largely diarrhoea), its role in CICI remains unknown, limiting microbial-based therapeutics or risk prediction strategies. Therefore, this review aims to synthesise and critically evaluate the evidence addressing the microbiota-gut-brain axis as a critical factor influencing the development of CICI.
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.
Background
Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several commonly used chemotherapy drugs including taxanes, vinca alkaloids, and platinum compounds. ...Development of CIPN is highly variable, both in self-reported symptoms and functional consequences, and can be severe enough to alter dose intensity.
Purpose
To describe the natural histories of both patient-reported symptoms of CIPN and functional impairments in breast cancer patients undergoing taxane-based chemotherapy.
Methods
Thirty-three breast cancer patients (32 female/1 male; 47.8 ± 11.2 years;
n
= 17 stage II/
n
= 16 stage III) were enrolled. Patients completed self-reports of symptoms and function (e.g., EORTC QLQ-CIPN20) and objective measures of physical function (i.e., balance and gait testing) in an outpatient oncology clinic at five timepoints: (1) baseline—prior to starting chemotherapy, (2–4) before starting subsequent chemotherapy cycles, and (5) 1–3 months after receiving their last taxane infusion.
Results
Significant negative changes in both patient-reported outcomes and objective functional measures were observed. Decreased balance was observed after the first chemotherapy cycle (28% increase in medial–lateral excursion of the center of pressure,
p
= 0.016) and progressed with cumulative exposure (43% increase,
p
< 0.001). Patients also demonstrated slower walking speeds (5% decrease,
p
= 0.003) as they progressed through treatment. These functional deficits were mirrored with increased patient-reported symptom severity for all EORTC QLQ-CIPN20 subscales (all
p
< 0.05).
Conclusion
This study longitudinally assessed patient-reported outcomes concurrently with balance and gait testing in patients undergoing taxane therapy. Taxane treatment was associated with the development of clinically relevant problems in both CIPN symptoms and patient function.
Despite the importance of chemotherapy-associated adverse events in oncology practice and the broad range of interventions available to mitigate them, limited systematic efforts have been made to ...identify, critically appraise and summarize the totality of evidence on the effectiveness of these interventions. Herein, we review the most common long-term (continued beyond treatment) and late or delayed (following treatment) adverse events associated with chemotherapy and other anticancer treatments that pose major threats in terms of survival, quality of life and continuation of optimal therapy. These adverse effects often emerge during and continue beyond the course of therapy or arise among survivors in the months and years following treatment. For each of these adverse effects, we discuss and critically evaluate their underlying biological mechanisms, the most commonly used pharmacological and non-pharmacological treatment strategies, and evidence-based clinical practice guidelines for their appropriate management. Furthermore, we discuss risk factors and validated risk-assessment tools for identifying patients most likely to be harmed by chemotherapy and potentially benefit from effective interventions. Finally, we highlight promising emerging supportive-care opportunities for the ever-increasing number of cancer survivors at continuing risk of adverse treatment effects.
Bone Health in Adult Cancer Survivorship Lustberg, Maryam B; Reinbolt, Raquel E; Shapiro, Charles L
Journal of clinical oncology,
10/2012, Letnik:
30, Številka:
30
Journal Article
Recenzirano
Optimizing health outcomes, including prevention of osteoporotic fractures, is essential for promoting the well-being of the growing number of cancer survivors. Medical providers who participate in ...the care of cancer survivors should be aware that various cancer treatments may cause bone loss, which can increase the risk of subsequent of osteoporosis. Healthy bone remodeling is a balanced and dynamic equation between new bone formation and bone resorption. Aging, natural menopause, and cancer treatments such as surgical oophorectomy, gonadotropin-releasing hormone agonists, chemotherapy-induced ovarian failure, androgen deprivation therapy, and aromatase inhibitors can all promote bone loss. The WHO Fracture Assessment Tool can be used as a clinical aid to assess an individual's osteoporotic fracture risk, with or without bone mineral density measurements obtained from dual-energy x-ray absorptiometry. Preventative strategies include adequate calcium and vitamin D supplementation and modifying risk factors such as alcohol intake, tobacco use, and lack of exercise. Bisphosphonate therapy and rank-ligand monoclonal antibody therapy are the most commonly used agents for management of bone loss resulting from cancer treatment. This review will summarize the mechanisms by which cancer treatments cause bone loss as well provide screening and treatment recommendations for the management of bone loss.
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