Updates in Cancer Cachexia: Clinical Management and Pharmacologic Interventions

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 beta 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.