消化道肿瘤恶病质的治疗

Cancer cachexia is a multifactorial syndrome characterized by involuntary weight loss, muscle mass reduction, and systemic inflammatory response, negatively impacting the quality of life and survival of cancer patients. In gastrointestinal tumors, cachexia prevalence can reach up to 80%, presenting a complex clinical challenge. This review aims to explore the efficacy of a multimodal approach integrating nutritional support and physical activity in cancer cachexia management. Targeted dietary strategies, such as a high-protein diet enriched with omega-3 and branched-chain amino acids (BCAAs), have proven effective in counteracting muscle loss and modulating inflammatory metabolism. Physical activity, particularly resistance training, contributes to preserving lean mass and improving physical function. However, current data suggest that no single strategy is sufficient to reverse cachexia, necessitating combined treatment with supportive pharmacological therapies, including progestogens, muscle metabolism modulators, and cytokine antagonists. Despite the evidence supporting these interventions, significant gaps remain, highlighting the need for randomized clinical trials to define the optimal therapeutic protocol for gastrointestinal cancer patients with cachexia.

To report the efficacy of anamorelin in patients with colorectal and gastric cancer with cachexia and in those receiving systemic chemotherapy. We retrospectively collected real-world data from patients diagnosed with colorectal and gastric cancers experiencing cachexia who were treated with anamorelin. We evaluated the efficacy of treatment by measuring the improvements in appetite and body weight (BW) gain. Between June 2021 and October 2022, 43 cancer patients with cachexia—23 with gastric cancer and 20 with colorectal cancer—were treated with anamorelin. Median observation period was 7.3 months. The participants were 25 males with median age of 71 years and median BMI of 19.7. The ECOG PS distribution was 4, 33, 6 for grades 0, 1, and 2, respectively. Seven patients received supportive care only, while 36 received anamorelin with chemotherapy. Thirty-four had received chemotherapy previously (≤ 2 regimens) and nine had received ≥ 3 regimens. Median anamorelin treatment duration was 2.8 months; overall survival was 7.3 months. After 3 weeks, 24 experienced appetite improvement and 21 gained weight; after 12 weeks, 20 experienced appetite improvement and 15 gained weight. Multivariate analysis showed that anamorelin treatment before second-line chemotherapy and colorectal cancer correlated with appetite improvement and weight gain at 3 weeks. In the univariate analysis, anamorelin treatment before second-line chemotherapy correlated with weight gain at 12 weeks and with improved overall survival in patients with weight gain at 12 weeks. Early anamorelin treatment contributes to appetite improvement and BW gain in colorectal and gastric cancers with cachexia.

Cancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported. We investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM. Seventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36–83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8–77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02). ANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice.

Background/Aim: Cachexia is a multifactorial syndrome that adversely affects the prognosis of patients with gastrointestinal cancer. Although anamorelin has been shown to improve appetite and body weight, the optimal timing of its initiation remains unclear. This study evaluated the effects of the timing of anamorelin initiation on nutritional recovery and clinical outcomes in patients with gastrointestinal cancer cachexia. Patients and Methods: We retrospectively reviewed 42 patients with gastric (n=17) or colorectal cancer (n=25) complicated by cachexia who received 100 mg of anamorelin once daily between August 2021 and December 2024. Changes in body weight, food intake, and nutritional status were assessed before and after anamorelin administration, and overall survival was analyzed according to the type of cancer. Results: Initially, patients had experienced a mean body weight loss of 15.9±1.7% relative to the pre-diagnosis baseline. After four weeks, mean body weight increased by 2.9% (p<0.001), food intake improved significantly from 30.5%±0.3% to 57.1%±0.5% (p<0.001), and the Patient-Generated Subjective Global Assessment short form (PG-SGA SF) score decreased from 12.3±0.4 to 10.3±0.9 (p=0.003). The median overall survival was 17.9 months for gastric cancer and 36.8 months for colorectal cancer, with no significant difference between the two groups (p=0.089). Conclusion: Anamorelin improved body weight, food intake, and nutritional status in patients with advanced gastrointestinal cancer cachexia. However, the modest degree of recovery suggests that earlier administration, before substantial weight and muscle loss, may maximize therapeutic benefits, support treatment continuity, and potentially improve survival outcomes. Therefore, early intervention should be considered in the clinical management of cancer cachexia.

(1) Background: Gastric cancer is a significant cause of cancer-related mortality worldwide. Weight loss and malnutrition associated with cancer are linked with increased mortality rates and reduced quality of life. Cancer cachexia, characterised by the loss of skeletal muscle, is associated with approximately 20% of cancer-related deaths and differs from malnutrition in that it cannot be fully reversed by nutritional support alone. It is now recognised that the primary pathophysiological process underlying cancer cachexia is chronic inflammation leading to increased calorie consumption. Current treatments that focus on nutritional supplementation, psychological counselling, appetite stimulation and reducing inflammation are lacking in efficacy. This review focuses on the evidence supporting the potential roles of natural anti-inflammatory products and their derivatives including fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate, ginger, resveratrol and Boswellia serrata in the management of gastric cancer cachexia. (2) Results: While natural anti-inflammatory products show promise in a number of in vitro and in vivo studies, there are only a small number of human studies available. Where present, the evidence base is heterogeneous, with varying study methodologies and outcomes. (3) Conclusions: Natural anti-inflammatory products represent a potential adjunctive therapy for gastric cancer cachexia. Further research, particularly well-designed clinical trials, is needed to elucidate their optimal role, dosing and safety profiles in the management of gastric cancer cachexia.

… In total, 127 patients with gastrointestinal cancer and cachexia were included in this study. Among these patients, four were excluded due to early loss to follow-up. Thus, data from a …

LBA12007 Background: Cancer cachexia arises from the interaction between the host and the tumour, triggering an inflammatory response that leads to weight and appetite loss, diminished physical activity, reduced treatment efficacy and survival. Combining interventions to address inflammation, weight loss, and physical activity is proposed as an effective strategy. Building on a promising pilot study, we conducted the MENAC (Multimodal Exercise Nutrition Anti-inflammatory Cachexia) trial to comprehensively evaluate this approach in patients with lung and pancreatic cancer undergoing systemic anti-cancer treatment (SACT). Methods: MENAC was an investigator-initiated, multicentre, open label, randomised phase 3 trial conducted at 17 sites in 4 countries. Patients with stage III or IV lung or pancreatic cancer receiving SACT with non-curative intent were randomly assigned (1:1) to a multimodal intervention consisting of nutritional counselling plus fish oil containing oral nutritional supplements, physical exercise [endurance and strength] and non-steroidal anti-inflammatory drugs [NSAIDs]) versus standard care. Randomisation was stratified by country, cancer type and stage. Primary Objective: To assess differences between arms in change in body weight. Secondary Objectives: To assess differences in muscle mass (measured by CT L3 technique) and physical activity (assessed through step counts using ActivPAL activity meter) between arms. Assessments were conducted at basline (pre-randomisation) and at endpoint (after 6 weeks). Results: From May 2015 to February 2022, 212 patients were enrolled (105 to multimodal treatment, 107 standard care). Over 6 weeks, weight stabilised in patients assigned to multimodal treatment compared with those assigned to standard care (mean weight change [SD] 0.05 kg [3.8] vs – 0.99 kg [3.2], respectively) with a mean difference in weight change of -1.04, 95 % CI -2.02 to -0.06, p=0.04. There was no conclusive difference in muscle mass (mean change [SD] -6.5cm2 [ 10.1] vs -6.3cm2 [11.9], p=0.93) or in mean step counts [SD] (-377.7 [2075] vs -458 [1858], p=0.89). There were 28 and 24 reported SAEs in the intervention and control arm respectively, no SUSARs were reported. Conclusions: A multimodal cachexia intervention stabilised weight compared to standard care at six weeks. There was no difference in physical activity or muscle mass between trial arms. Clinical trial information: NCT02330926 .

BACKGROUND: Cachexia (disease-related wasting) is a complex metabolic syndrome which occurs in people with chronic illnesses, including cancer, HIV/AIDS, kidney disease, heart disease, and chronic obstructive pulmonary disease (COPD). People with cachexia experience unintentional weight loss, muscle loss, fatigue, loss of appetite, and reduced quality of life. Multimodal interventions which work synergistically to treat the syndrome could lead to benefits. OBJECTIVES: To assess the benefits and harms of multimodal interventions aimed at alleviating or stabilising cachexia in people with a chronic illness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, and two trials registers in July 2024, together with reference checking, citation searching, and contact with study authors to identify studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults with or at risk of cachexia, comparing multimodal interventions combining two or more modalities (of pharmacology, nutrition, exercise) to treatment as usual, variation of the intervention, or unimodal intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened potentially eligible studies, extracted data, and assessed risk of bias (RoB 1). Primary outcomes were physical function, strength, and adverse events. Secondary outcomes were body composition and weight, quality of life (QoL), appetite, fatigue, and biochemical markers. We assessed the certainty of evidence with GRADE. MAIN RESULTS: = 79%; 3 studies, 411 participants), but the evidence is very uncertain. AUTHORS' CONCLUSIONS: The review found insufficient evidence to support or refute the use of multimodal interventions in managing cachexia. The certainty of the evidence was very low. Methodologically rigorous, well-powered RCTs with adequate interaction times are needed to assess the effectiveness of multimodal interventions in managing cachexia across chronic illnesses.

Simple Summary Cancer cachexia (CC) is a complex syndrome requiring a multimodal approach. Although a universally accepted definition and staging criteria for cancer cachexia remains elusive, there is general consensus regarding the importance of elements such as weight loss, muscle wasting, and poor appetite. Epidemic trends of obesity and overlapping conditions such as sarcopenia and frailty further complicate CC definition, staging, and relevant outcome measures. Despite progress in understanding the molecular mechanisms of CC, there is no single, consistently effective pharmacotherapy for CC and, unsurprisingly, there are variations among guidelines regarding management. Current pharmacologic research is focused on promising targeted treatments; however, a multimodal approach is likely to be more effective than any single therapeutic agent. This narrative review provides an update on non-pharmacologic and pharmacologic treatment and proposes a theoretical model for management of CC, which includes a multimodal therapeutic approach directed at the various mechanisms contributing to CC. Abstract Despite a better understanding of the mechanisms causing cancer cachexia (CC) and development of promising pharmacologic and supportive care interventions, CC persists as an underdiagnosed and undertreated condition. CC contributes to fatigue, poor quality of life, functional impairment, increases treatment related toxicity, and reduces survival. The core elements of CC such as weight loss and poor appetite should be identified early. Currently, addressing contributing conditions (hypothyroidism, hypogonadism, and adrenal insufficiency), managing nutrition impact symptoms leading to decreased oral intake (nausea, constipation, dysgeusia, stomatitis, mucositis, pain, fatigue, depressed mood, or anxiety), and the addition of pharmacologic agents when appropriate (progesterone analog, corticosteroids, and olanzapine) is recommended. In Japan, the clinical practice has changed based on the availability of Anamorelin, a ghrelin receptor agonist that improved lean body mass, weight, and appetite-related quality of life (QoL) compared to a placebo, in phase III trials. Other promising therapeutic agents currently in trials include Espindolol, a non-selective β blocker and a monoclonal antibody to GDF-15. In the future, a single therapeutic agent or perhaps multiple medications targeting the various mechanisms of CC may prove to be an effective strategy. Ideally, these medications should be incorporated into a multimodal interdisciplinary approach that includes exercise and nutrition.

Given the multi-faceted nature of cancer cachexia, a combination of pharmacologic and supportive measures such as exercise and nutrition seems intuitive to most clinicians. Clinical trials have also suggested that a multimodal approach to cancer cachexia (CC) is feasible and potentially effective. However, past trials have been limited by medications that were partially effective or had the potential for serious adverse events such as thromboembolism. We review new agents that have demonstrated efficacy in phase II trials or are involved in multi-center phase III studies. The advent of several recent phase II studies indicate that consistently effective, well-tolerated medications may soon be available for CC. These new agents target several mechanisms involved in CC, including food aversion, catabolism, and decreased anabolism. Several multi-center studies are expected to be actively recruiting this year. If these agents prove to be effective, individualized treatment may be possible, guided by individuals' phenotype and/or clinical biomarkers. Future research should also determine whether combination therapy (pharmacologic and/or non-pharmacologic) produces additive or synergistic benefits.

Cancer cachexia has substantial impacts on people's quality of life. There is no current gold standard treatment, but the complex pathophysiology of cachexia suggests that a multitargeted and individualised treatment approach is needed. We aimed to evaluate the extent to which multicomponent interventions have targeted the key features of cachexia and been tailored to individuals, and differential effects on quality of life.

Simple Summary Cachexia occurs in up to 80% of patients with cancer. Although cancer-associated cachexia dramatically decreases overall survival and quality of life, it is often overlooked. To make meaningful progress in identifying cancer cachexia earlier and finding treatments for this condition, Moffitt Cancer Center held its first Cachexia Working Group Retreat in 2022. This manuscript describes the priorities discussed at the retreat and highlights collaborations that arose afterward. Abstract For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes.

Objective Cancer cachexia occurs in 30%–80% of patients, increasing morbidity and mortality and impacting the health-related quality of life also for caregivers. Pharmacological interventions have been studied but have shown inconsistent effects on patients' lives in terms of relative outcomes and poor adherence to pharmacological treatment. We provide an overview of the evidence on non-pharmacological interventions for cancer cachexia. Methods We conducted a scoping review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension for scoping review (PRISMA-ScR). On September 21, 2022, plus an update on January 10, 2024, we searched MEDLINE, Embase, CINAHL, Cochrane, PsycINFO, and Scopus for 2012–2024. We excluded pharmacological interventions defined as “any substance, inorganic or organic, natural or synthetic, that can produce functional modifications, through a chemical, physicochemical or physical action.” Results The search retrieved 9308 articles, of which 17 were eligible. Non-pharmacological interventions included nutritional counseling, complementary therapies (acupuncture), rehabilitation, and psychoeducational/psychosocial support. The data showed small and heterogeneous samples and different disease localization and stages. Thirty-nine percent were multimodal interventions and aimed at patients, not families. The common primary outcomes were body weight and composition, biomarkers, quality of life, psychological suffering, and muscular strength. Only three studies focus on the patient-caregiver dyad. Conclusions Interventions on cancer cachexia should be multimodal and multiprofessional, proposed early, and aimed at quality of life outcomes. The caregiver's involvement is essential. Nurses can play an active role in managing cancer cachexia. More well-designed studies are needed to understand the efficacy and contents of non-pharmacological interventions. Systematic review registration The review protocol has been registered in the OSF registry (DOI: 10.17605/OSF.IO/H4A29).

… evidence supporting the use of multimodal interventions in the management of cancer … from cancer cachexia, to facilitate the prompt initiation of holistic, multimodal interventions (ie, …

Pharmacists’ roles in cachexia care are unclear. This study aimed to clarify the knowledge and practice of cachexia care and identify factors related to the practice of cachexia care among pharmacists. Information on the knowledge and practice of cachexia care was obtained. Components of practicing multimodal care were evaluated. Participants were categorized into two groups according to practicing multimodal care levels. Comparisons were made between the groups, and multiple regression analysis was employed. Of the 451 pharmacists, 243 responded. They were categorized into the Practicing group (n = 119) and Not practicing group (n = 124). Significant differences were observed for the number of advanced cancer patients/month, frequency of caring for them, and involvement in training programs on cachexia. The Practicing group had significantly better knowledge about cachexia. The Practicing group used guidelines, items, and symptoms more frequently to detect cachexia. The Practicing group tended to detect cachexia and initiate interventions in earlier phases and in patients with a better status. Multivariate logistic regression analysis showed that the most significant factor was the regular provision of care (odds ratio, 2.07; 95% confidence interval, 1.10–3.92). The regular provision of care was associated with the practice of multimodal care.

Cancer cachexia, a multifactorial metabolic syndrome characterized by severe muscle wasting and weight loss, contributes to poor outcomes across various cancer types but lacks a standardized, generalizable biomarker for early detection. We present a multimodal AI-based biomarker trained on real-world clinical, radiologic, laboratory, and unstructured clinical note data, leveraging foundation models and large language models (LLMs) to identify cachexia at the time of cancer diagnosis. Prediction accuracy improved with each added modality: 77% using clinical variables alone, 81% with added laboratory data, and 85% with structured symptom features extracted from clinical notes. Incorporating embeddings from clinical text and CT images further improved accuracy to 92%. The framework also demonstrated prognostic utility, improving survival prediction as data modalities were integrated. Designed for real-world clinical deployment, the framework accommodates missing modalities without requiring imputation or case exclusion, supporting scalability across diverse oncology settings. Unlike prior models trained on curated datasets, our approach utilizes standard-of-care clinical data, facilitating integration into oncology workflows. In contrast to fixed-threshold composite indices such as the cachexia index (CXI), the model generates patient-specific predictions, enabling adaptable, cancer-agnostic performance. To enhance clinical reliability and safety, the framework incorporates uncertainty estimation to flag low-confidence cases for expert review. This work advances a clinically applicable, scalable, and trustworthy AI-driven decision support tool for early cachexia detection and personalized oncology care.

Cancer‐associated cachexia is a multifactorial wasting disorder characterized by anorexia, unintentional weight loss (skeletal muscle mass with or without loss of fat mass), progressive functional impairment, and poor prognosis. This systematic literature review (SLR) examined the relationship between cachexia and survival in patients with colorectal or pancreatic cancer in recent literature. The SLR was conducted following PRISMA guidelines. Embase® and PubMed were searched to identify articles published in English between 1 January 2016 and 10 October 2021 reporting survival in adults with cancer and cachexia or at risk of cachexia, defined by international consensus (IC) diagnostic criteria or a broader definition of any weight loss. Included publications were studies in ≥100 patients with colorectal or pancreatic cancer. Thirteen publications in patients with colorectal cancer and 13 with pancreatic cancer met eligibility criteria. Included studies were observational and primarily from Europe and the United States. Eleven studies (42%) reported cachexia using IC criteria and 15 (58%) reported any weight loss. An association between survival and cachexia or weight loss was assessed across studies using multivariate (n = 23) or univariate (n = 3) analyses and within each study across multiple weight loss categories. Cachexia/weight loss was associated with a statistically significantly poorer survival in at least one weight loss category in 16 of 23 studies that used multivariate analyses and in 1 of 3 studies (33%) that used univariate analyses. Of the 17 studies demonstrating a significant association, 9 were in patients with colorectal cancer and 8 were in patients with pancreatic cancer. Cachexia or weight loss was associated with significantly poorer survival in patients with colorectal or pancreatic cancer in nearly two‐thirds of the studies. The classification of weight loss varied across and within studies (multiple categories were evaluated) and may have contributed to variability. Nonetheless, awareness of cachexia and routine assessment of weight change in clinical practice in patients with colorectal or pancreatic cancer could help inform prognosis and influence early disease management strategies.

Background: Cancer cachexia, often referred to as cancer wasting, is a multifactorial syndrome characterized by involuntary weight loss, muscle wasting, and systemic inflammation. It affects up to 80% of patients with advanced malignancy and is a major cause of morbidity and mortality. Despite increasing recognition, it remains underdiagnosed and inadequately treated. Objective: This meta-analysis aimed to evaluate the prevalence, clinical consequences, and effectiveness of interventions for cancer cachexia across malignancies. Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library up to December 2024. Randomized controlled trials (RCTs), cohort studies, and meta-analyses reporting prevalence, outcomes, or interventions in adult cancer patients were included. Studies were pooled using a random-effects model. Primary outcomes were prevalence and overall survival; secondary outcomes included treatment tolerance, quality of life, and intervention efficacy. Results: Forty-eight studies comprising 23,400 patients were analyzed. The pooled prevalence of cachexia was 49.2% (95% CI 43.1–54.8), highest in pancreatic (74%) and lung cancer (63%) populations. Cachexia was associated with a 41% higher risk of mortality (HR 1.41; 95% CI 1.23–1.61) and reduced chemotherapy tolerance (RR 1.38). Nutritional interventions alone were insufficient, whereas multimodal approaches (nutrition, pharmacologic agents, exercise) improved weight stabilization and quality of life. Anamorelin drug showed moderate efficacy in increasing lean body mass, though survival benefit remained unproven. Conclusion: Cancer cachexia is highly prevalent and clinically significant, yet interventions remain suboptimal. Early identification and multimodal treatment should be integrated into oncology practice. Future research must focus on biomarkers, standardization of diagnostic criteria, and novel therapeutic targets.

Objective Assessing the impact of perioperative enteral nutrition (EN) on postoperative acute muscle atrophy following radical gastrectomy for gastric cancer(GC) (with changes in skeletal muscle mass as the primary outcome indicator). Methods Patients who underwent GC surgery at the Department of Gastrointestinal Oncology Surgery in a top-tier hospital in Nanjing were selected for the study. The control group, consisting of patients treated between January and June 2023, received routine perioperative nutritional management. The experimental group, consisting of patients treated between July and December 2023, followed a preoperative combined with early postoperative EN program. skeletal muscle mass, grip strength, 6-meter walk test speed, and body weight were compared between the two groups 7 d postoperatively. Results The intervention significantly reduced the loss of skeletal muscle mass, grip strength, and body weight from baseline (p<0.01). However, no significant differences in 6-meter walk test speed were observed between the two groups. After adjusting for confounding factors such as age, gender, nutritional risk screening 2002(NRS 2002) score, education level, diabetes comorbidity, tumor staging, surgical approach, intraoperative blood loss, and operation time, multivariate linear regression analysis showed that the EN program independently influenced the loss rates of skeletal muscle mass, grip strength, and body weight (p<0.01). Conclusion The perioperative EN program for GC developed in this study enables medical staff to efficiently gather relevant information, providing a more comprehensive and holistic approach to EN for GC patients. The program effectively reduces postoperative acute muscle wasting, grip strength loss, and weight loss. This study provides a reference for clinical perioperative EN management in GC patients.

The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.

Cancer cachexia, a systemic multifactorial syndrome that affects survival prognosis, occurs in 80% of patients with advanced cancer. Patients with cancer cachexia experience progressive functional disability and persistent loss of skeletal muscle mass associated with reduced quality of life. Cancer cachexia requires multidisciplinary early intervention, including drugs, exercise, nutrition, and psychotherapy. Anamorelin is an oral drug with ghrelin-like effects, including significant appetite stimulation, increase in food intake and weight, and stimulation of growth hormone secretion. This review provides an overview of basic drug information and clinical trial data on anamorelin, focusing on its role in the treatment of cancer cachexia, with the aim of achieving more effective anamorelin administration. In several randomized, double-blind, placebo-controlled clinical trials, anamorelin significantly improved lean body mass and appetite in patients with cancer cachexia. However, no improvement was observed in motor function (handgrip strength and 6-minute walk test). Clinical trials of anamorelin have shown approximately consistent trends in efficacy, but decisions on whether or not to approve anamorelin vary internationally. The treatment of cancer cachexia, including with anamorelin, requires consideration of the selection of target patients, burden of treatment on patients, and assessment tools used by healthcare providers that may affect treatment outcomes. Based on several retrospective datasets, the initiation of anamorelin at earlier stages of cancer cachexia, combined with nutritional and exercise therapy, should be considered. However, current evidence is insufficient, and results of future studies are awaited.

Background Cachexia is a leading cause of death among individuals with advanced cancer, yet effective pharmacological treatments are lacking. In this single-center retrospective study, we aimed to investigate the efficacy and safety of tocilizumab for the treatment of cancer cachexia accompanied by systemic hyperinflammation. Methods Data were collected from 20 patients treated with tocilizumab and a control group of 20 patients matched for age, sex, and comorbidities. Both groups received corticosteroids. In the tocilizumab treatment group, patients received a single dose of tocilizumab (8 mg/kg, maximum 800 mg) in combination with corticosteroids. Weight, body mass index, liver metastasis, Eastern Cooperative Oncology Group score, patient-generated subjective global assessments, the Anorexia/Cachexia Subscale of the Functional Assessment of Anorexia/Cachexia Therapy, handgrip strength, neutrophil-to-lymphocyte ratio, and the C-reactive protein, hemoglobin, prealbumin, and albumin levels were recorded in both groups. Results Tocilizumab treatment favorably influenced the levels of patient biomarkers (p<0.05), ameliorated systemic inflammation, and demonstrated enhanced clinical short-term efficacy compared to the control group, including rates of symptomatic relief (60% vs. 20%, p = 0.024), improvement of serum PAB and ALB (70% vs. 25%, p = 0.004), weight gain >2% (45% vs. 15%, p = 0.038), and improvement of grip strength and 6-m walk speed (p<0.05). Treatment with tocilizumab was generally safe, with no observed increase in infection rates (10% vs. 15%, p = 0.633) or intensive care unit admissions (10% vs. 25%, p = 0.405), and was more favorable for restarting antitumor therapy (70% vs. 35%, p = 0.027). Conclusions Tocilizumab, in combination with corticosteroids, is favorable for alleviating cancer cachexia with systemic hyperinflammation, despite the small sample size. Thus, this combination holds great potential as a novel strategy for treating cancer cachexia with systemic hyperinflammation.

PURPOSE OF REVIEW Cancer cachexia is a complex multiorgan wasting syndrome that negatively impacts on cancer patient's survival and quality of life. Standard nutritional support is considered insufficient to counteract cachexia, and no approved nutritional approach or standard of care for cachexia exists so far. This review highlights recent reports focused on nutrition, aimed at sparing skeletal muscle and targeting molecular pathways underlying cachexia with specific supplements. RECENT FINDINGS In animal models of cancer cachexia, branched-chain amino acids (BCAAs) help restore skeletal muscle proteostasis. In combination with the alanine dipeptide, with strong proteinogenic potential, BCAAs enhance anabolic signaling and suppress proteolysis via mTOR. α-ketoisocaproate exerts additional protective effects against muscle loss by targeting the Akt/FoxO3a and myostatin signaling. Methionine and the derivative SAM improve muscle status via epigenetic control and REDD1 suppression. L-carnitine shows multitarget functions, including muscle proteostasis control, inflammation attenuation, and reduced muscle fibrosis. Omega-3 polyunsaturated fatty acids show anti-inflammatory properties, improve the nutritional status, and prevent adipose tissue browning. SUMMARY Overall, recent findings in preclinical and partly in clinical studies indicate that nutrient-based interventions target complementary cancer cachexia alterations. It is likely that combinatorial approaches, integrating several specific nutrients, will provide an effective base for managing cancer patients during the long journey of the disease, building future interventions against cancer cachexia.

Real-world data on the effectiveness of anamorelin in managing cancer cachexia remains limited, particularly as its availability is currently restricted to Japan. In the present study, anamorelin use in cancer cachexia management was retrospectively evaluated, focusing on patient characteristics and survival after both short- and long-term use. Patients prescribed anamorelin between August 2021 and January 2024 at the Saitama Canc2er Center (Ina, Japan) were included. Medical records were reviewed to collect baseline characteristics at anamorelin treatment initiation. The patients were divided into two groups: short- and long-treatment groups (STT and LTT, respectively). Overall, 60 and 69 patients were included in the STT and LTT groups, respectively. Significant intergroup differences were found in age (P=0.021), gastric cancer incidence rate (P=0.013), albumin level of <3.5 g/dl (P=0.044) and Eastern Cooperative Oncology Group performance status score (P=0.008). The longest median time from diagnosis to anamorelin treatment initiation was observed for colorectal cancer, while the longest median anamorelin treatment duration was observed for lung cancer. The median survival durations during anamorelin treatment were 49 and 142 days in the STT and LTT groups, respectively (P<0.001). The corresponding median survival durations after anamorelin treatment termination in the STT and LTT groups were 38 and 34 days (P=0.554), respectively. Anamorelin treatment duration influenced patient survival, with post-discontinuation survival being ~1 month, regardless of treatment length.

Cancer cachexia is a complex systemic wasting syndrome. Nutritional mechanisms that span energy intake, nutrient metabolism, body composition, and energy balance may be impacted by, and may contribute to, the development of cachexia. To date, clinical management of cachexia remains elusive. Leaning on discoveries and novel methodologies from other fields of research may bolster new breakthroughs that improve nutritional management and clinical outcomes. Characteristics that compare and contrast cachexia and obesity may reveal opportunities for cachexia research to adopt methodology from the well-established field of obesity research. This review outlines the known nutritional mechanisms and gaps in the knowledge surrounding cancer cachexia. In parallel, we present how obesity may be a different side of the same coin and how obesity research has tackled similar research questions. We present insights into how cachexia research may utilize nutritional methodology to expand our understanding of cachexia to improve definitions and clinical care in future directions for the field.

Background The objective of this study is to investigate the efficacy of megestrol acetate (MA) in treating cancer cachexia from multiple dimensions. Methods In this prospective, non-randomized study, 97 patients with cancer cachexia were allocated to either a control group (n = 33, regular diet) or an MA group (n = 64, regular diet plus MA 320 mg/day) for 2 months. The primary endpoints were nutritional indices, including weight, BMI, total skeletal muscle mass, and fat mass. Secondary endpoints included inflammatory markers (CRP, IL-6, TNF-α), immune parameters (CD4+, CD8+ T cells), cancer-related fatigue (assessed by the Cancer Fatigue Scale), and quality of life (QOL). Results Compared to baseline, the MA group exhibited significant improvements in body weight, BMI, fat mass, prealbumin (PA), albumin (ALB), and hemoglobin (Hb), coupled with a significant reduction in IL-6 levels and all domains of cancer-related fatigue (somatic, cognitive, affective, and total). Between-group analyses demonstrated that the MA group achieved significantly greater improvements in weight, BMI, fat mass, PA, ALB, and Hb. Skeletal muscle mass was maintained in the MA group, whereas the control group experienced a significant loss, resulting in a significant between-group difference. Furthermore, the MA group showed markedly greater reductions in all fatigue domain scores and a more substantial improvement in QOL. No significant between-group differences were observed for most inflammatory or immune markers. The intervention was well-tolerated with no reported drug-related adverse events. Conclusion MA significantly improves nutritional status and ameliorates cancer-related fatigue, thereby enhancing the quality of life in patients with cancer cachexia. Our findings provide robust evidence supporting the multi-dimensional benefits of MA in cachexia management, extending beyond mere weight gain to include muscle mass preservation and patient-centered symptom relief.

… , thalidomide, and megestrol acetate may positively affect lean … nutrition supplements with dietary counseling and exercise … interventions integrating exercise with nutrition may hold even …

This editorial and the accompanying article summarize evidence-based guidelines that can inform dietary recommendations in oncology practices.

Cachexia is a multifactorial metabolic syndrome characterized by weight and skeletal muscle loss caused by underlying illnesses such as cancer, heart failure, and renal failure. Inflammation, insulin resistance, increased muscle protein degradation, decreased food intake, and anorexia are the primary pathophysiological drivers of cachexia. Cachexia causes physical deterioration and functional impairment, loss of quality of life, lower response to active treatment, and ultimately morbidity and mortality, while the difficulties in tackling cachexia in its advanced phases and the heterogeneity of the syndrome among patients require an individualized and multidisciplinary approach from an early stage. Specifically, strategies combining nutritional and exercise interventions as well as pharmacotherapy that directly affect the pathogenesis of cachexia, such as anti‐inflammatory, metabolism‐improving, and appetite‐stimulating agents, have been proposed, but none of which have demonstrated sufficient evidence to date. Nevertheless, several agents have recently emerged, including anamorelin, a ghrelin receptor agonist, growth differentiation factor 15 neutralization therapy, and melanocortin receptor antagonist, as candidates for ameliorating anorexia associated with cancer cachexia. Therefore, in this review, we outline cancer cachexia‐associated anorexia and its pharmacotherapy, including corticosteroids, progesterone analogs, cannabinoids, anti‐psychotics, and thalidomide which have been previously explored for their efficacy, in addition to the aforementioned novel agents, along with their mechanisms.

In patients receiving anti‐cancer treatment, cachexia results in poorer oncological outcomes. However, there is limited understanding and no systematic review of oncological endpoints in cancer cachexia (CC) trials. This review examines oncological endpoints in CC clinical trials.

REGISTRATION PROSPERO registration no. CRD420251131074.

… Gastrointestinal tumors represent a significant proportion of malignant neoplasms worldwide. Sarcopenia … loss of skeletal muscle mass and function, sarcopenia has been associated …

Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut‐off value of SO in patients with gastrointestinal cancer among Chinese population.

OBJECTIVE The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia. METHODS This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model. RESULTS The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847. CONCLUSIONS The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia.

OBJECTIVE The impact of sarcopenia on the efficacy of immune checkpoint inhibitors (ICI) in gastrointestinal cancer (GIC) patients remains uncertain in clinical practice. Hence, this study aims to investigate the potential correlation between sarcopenia and the clinical outcomes of GIC patients treated with ICIs. METHODS To gather pertinent studies, a systematic literature search was implemented across multiple databases, including PubMed, Embase, the Cochrane Library, and Google Scholar. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), measured with the hazard ratio (HR). And the secondary outcomes, including disease control rate (DCR), overall response rate (ORR), and adverse events (AE), were evaluated with the odd ratio (OR). RESULTS A total of 13 articles involving 1294 patients were collected for this analysis. The pooled results revealed that GIC patients with sarcopenia had significantly poorer OS (HR = 1.697, 95% CI = 1.367-2.106, p < 0.001) and PFS (HR: 1.551, 95% CI: 1.312-1.833, p < 0.001), and lower ORR (OR = 0.594, 95% CI = 0.388-0.909, p = 0.016) and DCR (OR: 0.553, 95% CI: 0.360-0.850, p = 0.007) compared to those without sarcopenia. However, sarcopenia did not increase the incidence of treatment-related adverse events compared with non-sarcopenia (OR = 1.377, 95% CI = 0.693-2.737, p = 0.361). According to subgroup analysis, the association between sarcopenia and the therapeutic effect of ICI on patients with primary liver cancer or gastric cancer was consistent with the above findings. CONCLUSION Sarcopenia is significantly correlated with poorer treatment response and worse long-term efficacy in GIC patients treated with ICIs. Moreover, sarcopenia does not increase the incidence of adverse events.

… Cancer anorexia-cachexia syndrome is difficult to treat, and a single intervention is unlikely … Cancer Network Palliative Care guidelines recommend assessment and treatment of …

Abstract The anorexia–cachexia syndrome (ACS) is characterized by loss of appetite and unintentional weight loss. Important clinical outcomes are associated with ACS including increased risk of chemotherapy side effects, decreased survival, and quality of life. Because ACS is driven by complex metabolic mechanisms and a chronic pro-inflammatory response, the weight loss and muscle wasting cannot be reversed by conventional nutritional supplementation alone. However, insufficient intake of calories and protein exacerbate weight loss experienced by patients with ACS, while physical inactivity accelerate muscle wasting. In addition, uncontrolled symptoms, such as pain, mucositis, nausea, early satiety, and depression aggravate poor nutritional intake and are known as nutrition impact symptoms. Addressing these potentially reversible contributors to ACS requires an interdisciplinary team (IDT) effort including oncologists, palliative medicine, rehabilitation clinicians, dietitians, and psychologists. The composition and leadership of the team depends on institutional support and the patient population being treated (eg, advanced cancer vs peri-operative rehabilitation vs geriatric). Because patients may be burdened by frequent visits to multiple healthcare providers and a special skill set is required of the IDT to address ACS—measuring caloric and protein intake, assessing body composition, optimal symptom management, and providing psycho-social support–a specialized clinic would be ideal. As more effective anti-cachexia agents are being developed, nutritional rehabilitation programs and cachexia clinics could facilitate incorporation of novel treatments into multimodal management of ACS. The narrative review highlights the management of nutrition impact symptoms and the potential benefits and challenges of specialized nutrition rehabilitation programs and cachexia clinics.

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.

Background Cancer anorexia-cachexia syndrome (CACS) is a multifactorial syndrome characterized by weight loss and muscle wasting that leads to impaired physical function, decreased tolerance to anticancer therapies, and reduced survival rates. Megestrol acetate (MA) is an important pharmacological intervention for CACS. Nanocrystalline MA (MA-ES), leveraging nanocrystal technology, enhances bioavailability and absorption rates. Previous research has demonstrated that MA-ES could result in a more significant weight increase than non-MA-ES. However, its efficacy and safety in Chinese patients with cancer require further evaluation and validation in real-world clinical settings. The purpose of this study was to evaluate the therapeutic efficacy and safety of MA-ES and MA tablets in hormone-insensitive patients with CACS. Methods This prospective, multi-cohort, multicenter, real-world clinical study compared MA-ES and MA tablets in terms of efficacy and safety for hormone-insensitive patients with CACS (excluding breast cancer, endometrial cancer, and prostate cancer). The MA-ES group received 5 mL/day (625 mg/day), while the MA tablet group received 800 mg/day. CACS patients who completed three cycles of MA-ES at 5 mL/day or MA tablets at 800 mg/day were included in the propensity score matching (PSM) analysis (one cycle was defined as 28 days, with ≥21 days considered as completion of one cycle). PSM (1:2 ratio, caliper width 0.1) was used to mitigate the confounding factors. Patients were treated for three consecutive cycles, with each cycle lasting 4 weeks. The primary endpoint was the change in body weight from baseline at 12 weeks. Additionally, appetite, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scores, and safety were also evaluated. The standardized mean differences (SMDs) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results Between October 15, 2024 and February 28, 2025, 126 patients met the screening criteria and were enrolled in the analysis, with 76 in the MA-ES group and 50 in the MA tablet group. SMD of each matched variable was less than 0.10. At week 12, the MA-ES group exhibited an average weight gain of 4.49 kg, significantly higher than the 2.10 kg observed in the MA tablet group, with a mean difference of 2.39 kg (95% confidence interval: 1.33–3.45; P<0.001). Furthermore, at week 12, the MA-ES group demonstrated significantly greater proportions of participants with improved appetite (81.6% vs. 42.0%; P<0.001) and enhanced global health status (P<0.001). Conclusions MA-ES administered at 625 mg/day for over three cycles may offer superior weight gain benefits compared to the conventional MA tablets at 800 mg/day in hormone-insensitive patients with CACS. Moreover, MA-ES appears to provide more significant advantages in improving appetite and overall quality of life. Therefore, MA-ES may offer better clinical benefits compared to MA tablets for CACS patients.

OBJECTIVE Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients. METHODS A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires. RESULTS After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05). CONCLUSIONS Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.

There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia–cachexia syndrome. This review aimed to examine the dose–response effect of MA supplementation in patients with cancer‐associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer‐associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random‐effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [−0.11, 1.38], P = 0.093, I2 = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short‐term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose–response meta‐analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I2 = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I2 = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [−0.05, 0.64], P = 0.096, I2 = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [−0.09, 0.36], P = 0.236, I2 = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes.

Background: Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. Methods: A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Results: Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Conclusions: Low dose olanzapine (2.5–5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients.