Pharmacological Treatments for Cancer-Related Anorexia-Cachexia Syndrome: An Umbrella Review of Systematic Reviews and Meta-Analyses Publisher Pubmed



Zamanian N ; Mohajerani A ; Barkhordar M ; Rahimlou M ; Amiri Khosroshahi R ; Talebi S ; Azari M ; Soleimani A ; Mohammadi H
Source: Nutrition and Cancer Published:2026

Abstract

Cancer-related anorexia–cachexia syndrome (CACS) is a multifactorial disorder characterized by progressive weight loss, muscle wasting, and systemic inflammation, leading to reduced survival and quality of life. Despite various pharmacological interventions, their efficacy and safety remain unclear. We conducted an umbrella review of systematic reviews and meta-analyses of randomized controlled trials evaluating pharmacological treatments for CACS, searching PubMed, Scopus, and Web of Science up to May 2025. Methodological quality was assessed using AMSTAR 2, and certainty of evidence was evaluated with GRADE. Primary outcomes included body weight, lean body mass, appetite, quality of life, and adverse events. Seventeen reviews covering 61 trials (6,075 participants) were included. Anamorelin consistently improved lean body mass, grip strength, and body weight. Megestrol acetate modestly enhanced quality of life without consistent effects on weight or appetite, whereas omega-3 fatty acids showed small benefits, and cannabinoids were largely ineffective. Overall, most outcomes were of low or very low certainty due to methodological limitations and heterogeneity. Anamorelin appears most promising for improving muscle mass and selected clinical outcomes in CACS. High-quality, long-term trials and multimodal interventions integrating pharmacological, nutritional, and supportive strategies are urgently needed. Registration: PROSPERO registration no. CRD420251131074. © 2026 Taylor & Francis Group, LLC.