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Journal of Cachexia, Sarcopenia and... Oct 2023In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function...
In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
Topics: Humans; Cachexia; Hand Strength; Neoplasms; Quality of Life; Research Design
PubMed: 37671529
DOI: 10.1002/jcsm.13321 -
Oncology (Williston Park, N.Y.) Jan 2017Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not... (Review)
Review
Weight loss is distressing to cancer patients and caregivers. Anorexia/cachexia syndrome is characterized by lipolysis and the loss of lean body mass, and is not reversible by increasing caloric intake. The pathophysiology of cancer cachexia is complex and includes symptoms that impact caloric intake, as well as chronic inflammation, hypermetabolism, and hormonal alterations. Cancer patients require routine screening for cachexia and, ideally, interventions should be initiated in the early stages of weight loss. No guidelines exist for the treatment of cancer cachexia. Appetite stimulants, such as megestrol acetate and glucocorticoids, have been shown to increase appetite and weight; however, single pharmaceutical interventions alone for cachexia do not result in meaningful functional outcomes. In the future, clinicians should consider multimodality treatment that is personalized for each patient. These interventions would include nutritional counseling, assessing and treating symptoms that have an impact on caloric intake, and a rational combination of pharmacologic approaches directed at underlying pathophysiology. Use of an appetite stimulant could be considered for patients who exhibit decreased appetite. Treatment with an anti-inflammatory agent should be considered for patients with elevated C-reactive protein, and hormonal alterations resulting from anti-cachexia therapy should be thoughtfully addressed.
Topics: Appetite Stimulants; Cachexia; Energy Intake; Humans; Neoplasms; Nutritional Support; Practice Guidelines as Topic
PubMed: 28090619
DOI: No ID Found -
Nutrition in Clinical Practice :... Feb 2023The majority of evidence on efficacy of appetite-stimulating medications is limited to specific populations and the outpatient treatment setting. However, hospitalized... (Review)
Review
BACKGROUND
The majority of evidence on efficacy of appetite-stimulating medications is limited to specific populations and the outpatient treatment setting. However, hospitalized adults remain at risk for poor appetite and inadequate intake.
METHOD
The purpose of this review was to assess recent evidence on the efficacy of dronabinol, megestrol acetate, and mirtazapine (used to stimulate appetite) on promoting change in intake; somatic symptoms, such as appetite and nausea; and weight change during hospital stay. The population was limited to hospitalized adults or adults who demonstrated a need for appetite stimulation during hospitalization.
RESULTS
Of the 382 articles screened, four met inclusion criteria (one randomized control trial, two retrospective cohort studies, and one retrospective case series). Based on the studies included, these appetite stimulants have limited efficacy on improving appetite and meal intake. There was no significant change in weight.
CONCLUSION
Current data lack standardization, generalizability, and comparability, and higher quality evidence is needed before conclusions can be identified on the efficacy of dronabinol, megestrol acetate, and mirtazapine in the inpatient setting.
Topics: Humans; Adult; Appetite; Megestrol Acetate; Retrospective Studies; Dronabinol; Mirtazapine; Appetite Stimulants
PubMed: 35076955
DOI: 10.1002/ncp.10839 -
Journal of Oncology Practice Nov 2016Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in... (Review)
Review
Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.
Topics: Biomarkers; Body Composition; Cachexia; Exercise; Humans; Neoplasms; Weight Loss
PubMed: 27858548
DOI: 10.1200/JOP.2016.016832 -
Journal of Cachexia, Sarcopenia and... Apr 2018We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of... (Meta-Analysis)
Meta-Analysis Review
We provide a systematic review and meta-analysis on the efficacy, tolerability, and safety of cannabinoids in palliative medicine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus, and http://clinicaltrials.gov, and a selection of cancer journals were searched up until 15th of March 2017. Of the 108 screened studies, nine studies with a total of 1561 participants were included. Overall, the nine studies were at moderate risk of bias. The quality of evidence comparing cannabinoids with placebo was rated according to Grading of Recommendations Assessment, Development, and Evaluation as low or very low because of indirectness, imprecision, and potential reporting bias. In cancer patients, there were no significant differences between cannabinoids and placebo for improving caloric intake (standardized mean differences [SMD]: 0.2 95% confidence interval [CI]: [-0.66, 1.06] P = 0.65), appetite (SMD: 0.81 95% CI: [-1.14, 2.75]; P = 0.42), nausea/vomiting (SMD: 0.21 [-0.10, 0.52] P = 0.19), >30% decrease in pain (risk differences [RD]: 0.07 95% CI: [-0.01, 0.16]; P = 0.07), or sleep problems (SMD: -0.09 95% CI: [-0.62, 0.43] P = 0.72). In human immunodeficiency virus (HIV) patients, cannabinoids were superior to placebo for weight gain (SMD: 0.57 [0.22; 0.92]; P = 0.001) and appetite (SMD: 0.57 [0.11; 1.03]; P = 0.02) but not for nausea/vomiting (SMD: 0.20 [-0.15, 0.54]; P = 0.26). Regarding side effects in cancer patients, there were no differences between cannabinoids and placebo in symptoms of dizziness (RD: 0.03 [-0.02; 0.08]; P = 0.23) or poor mental health (RD: -0.01 [-0.04; 0.03]; P = 0.69), whereas in HIV patients, there was a significant increase in mental health symptoms (RD: 0.05 [0.00; 0.11]; P = 0.05). Tolerability (measured by the number of withdrawals because of adverse events) did not differ significantly in cancer (RD: 1.15 [0.80; 1.66]; P = 0.46) and HIV patients (RD: 1.87 [0.60; 5.84]; P = 0.28). Safety did not differ in cancer (RD: 1.12 [0.86; 1.46]; P = 0.39) or HIV patients (4.51 [0.54; 37.45]; P = 0.32) although there was large uncertainty about the latter reflected in the width of the CI. In one moderate quality study of 469 cancer patients with cancer-associated anorexia, megestrol was superior to cannabinoids in improving appetite, producing >10% weight gain and tolerability. In another study comparing megestrol to dronabinol in HIV patients, megestrol treatment led to higher weight gain without any differences in tolerability and safety. We found no convincing, unbiased, high quality evidence suggesting that cannabinoids are of value for anorexia or cachexia in cancer or HIV patients.
Topics: Cannabinoids; Humans; Palliative Medicine
PubMed: 29400010
DOI: 10.1002/jcsm.12273 -
Pharmaceuticals (Basel, Switzerland) Feb 2022Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss... (Review)
Review
Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss of body weight, and lower quality of life. Although drugs such as megestrol acetate and cyproheptadine are used to decrease this severe feeding disorder, they can also induce side effects, such as diarrhea and somnolence, which limit their widespread use. Various types of herbal medicines have long been used to prevent and treat numerous gastrointestinal tract diseases; however, to date, no study has been conducted to analyze and summarize their effects on cisplatin-induced anorexia. In this paper, we analyze 12 animal studies that used either a single herbal medicine extract or mixtures thereof to decrease cisplatin-induced anorexia. Among the herbal medicines, Ginseng Radix was the most used, as it was included in seven studies, whereas both Glycyrrhizae Radix et Rhizoma and Angelicae Gigantis Radix were used in four studies. As for the mechanisms of action, the roles of serotonin and its receptors, cytokines, white blood cells, ghrelin, and leptin were investigated. Based on these results, we suggest that herbal medicines could be considered a useful treatment method for cisplatin-induced anorexia.
PubMed: 35215322
DOI: 10.3390/ph15020208 -
World Journal of Gastrointestinal... Apr 2015It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal... (Review)
Review
It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.
PubMed: 25897346
DOI: 10.4251/wjgo.v7.i4.17 -
Current Pharmaceutical Design 2018Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients... (Review)
Review
Cancer cachexia, one of the metabolic syndromes caused by cancer, is a devastating and miserable condition encountered in more than 50% of terminal cancer patients presenting with significant weight loss associated with skeletal muscle atrophy and fat loss. Though cachexia may account for up to 20% of cancer deaths, no significant treatment is still lacking and is of urgent unmet medical need in cancer treatment. Therefore, understanding the underlying molecular mechanisms is essential for anticipating therapeutic approaches. Since the primary events driving cachexia are mediated via either the central nervous system relatedor inflammation related-anorexia, hypoanabolism, and hypercatabolism, therapy usually targets nutritional support to compensate reduced food intake along with some anti-inflammatory agents to cover specific inflammation-related metabolic derangement, and encourages exercise to supplement reduced physical activity, but all proven to be not so effective so far. Therefore, combination therapies such as a standard multi-modal package including an anorexic agent, megestrol acetate, and anti-inflammatory agent coupled with the development of potential novel therapeutics promise a new era in rescuing patients from cancer cachexia. In this review, we propose the potential application of BPC157, one of the active cytoprotective agents isolated from gastric juices for cancer cachexia. Before clinical trial, we introduced the evidence showing BPC157 rescued from cancer cachexia supported with explored mode of actions.
Topics: Animals; Anti-Ulcer Agents; Cachexia; Gastric Juice; Humans; Neoplasms; Peptide Fragments; Proteins
PubMed: 29898649
DOI: 10.2174/1381612824666180614082950 -
Advances in Clinical and Experimental... Feb 2018Advanced cancer patients in hospice are at notably increased risk of venous thromboembolism (VTE) due to age, local and distal advancement of the malignancy and bed... (Review)
Review
Advanced cancer patients in hospice are at notably increased risk of venous thromboembolism (VTE) due to age, local and distal advancement of the malignancy and bed confinement, among other factors. Asymptomatic VTE prevalence among palliative care patients has been found to reach 50%, whereas the clinically overt form occurs in 10%. Hospice patients are frequently given medications increasing VTE risk, for instance megestrol which is a drug commonly used in cancer cachexia. Many of the available guidelines encourage the implementation of thromboprophylaxis (TPX) in cancer patients, e.g., in the perioperative period or over the course of chemotherapy. However, concerning patients remaining under hospice care where the priority goal is not life extension but assurance of the best possible quality of life (QoL), the main benefit from the TPX would be a decrease in the risk of symptom burden associated with VTE, i.e., pain, edema or dyspnea. Nevertheless, studies performed on a sufficiently large study group, which could unequivocally determine the influence of anticoagulation on VTE symptom burden in hospice patients, are still lacking. VTE prophylaxis is challenging for many reasons: its unknown effect on QoL, vague risk of its discontinuation, and risk of bleeding complications which is additionally increased in conditions prevalent in hospice population, i.e., malnutrition, renal or liver insufficiency. So far, most of the guidelines issued by oncological societies do not precisely refer to the problem of TPX in hospice patients. Therefore, the decisions on the implementation of anticoagulation should be taken individually, with previous assessment of VTE risk, comorbidities and possible hemorrhagic complications.
Topics: Anticoagulants; Hospice Care; Hospices; Humans; Neoplasms; Palliative Care; Quality of Life; Risk Factors; Venous Thromboembolism
PubMed: 29521074
DOI: 10.17219/acem/64593 -
Expert Opinion on Investigational Drugs 2016About one third of patients with endometrial cancer (EC) relapse and face a limited prognosis, if surgery or radiotherapy are not feasible. The remaining therapeutic... (Review)
Review
INTRODUCTION
About one third of patients with endometrial cancer (EC) relapse and face a limited prognosis, if surgery or radiotherapy are not feasible. The remaining therapeutic options are chemotherapy and endocrine therapy.
AREAS COVERED
This review summarizes the development of the first selective estrogen receptor (ER) down-regulator fulvestrant. This article provides its mechanism of action, pharmacokinetics and the available preclinical and clinical data. Furthermore, this review provides an overview of the market of treatments for recurrent or metastatic EC (RMEC) while also taking into account studies of fulvestrant in metastatic breast cancer.
EXPERT OPINION
Even if fulvestrant showed only marginal activity in two phase II trials, it shouldn't be abandoned but instead further developed in EC. Firstly, the dose of fulvestrant used in these trials was too low from today's point of view. Secondly, the available literature on other endocrine agents is full of limitations and does not provide a gold standard. Furthermore, given the activity of mTOR inhibitors in EC, there may also be synergistic effects, given the cross-regulation of ER and the PI3K/AKT/mTOR pathway. The authors suggest that a prospective, phase II trial in ER positive RMEC would help to further explore the efficacy and tolerability of fulvestrant together with a mTOR inhibitor.
Topics: Animals; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Estradiol; Female; Fulvestrant; Humans
PubMed: 26882357
DOI: 10.1517/13543784.2016.1154532