What are the criteria for response to cachexia treatment?

Jeffrey Crawford


The treatment of cancer cachexia remains an unmet medical need. One of the barriers to the development and approval of effective interventions has been the lack of agreement on the proper endpoints for study. The international consensus definition of cancer cachexia focuses on 3 major components of the syndrome. This includes altered body composition characterized specifically by loss of skeletal muscle mass. The muscle loss in turn is a result of negative protein and energy balance secondary to reduced food intake and abnormal metabolism. The result of muscle loss is progressive functional impairment. The assessment of interventions for cancer cachexia should include measures of all 3 components of cancer cachexia. For patients with cancer cachexia, body composition measurements of lean body mass (LBM) and fat mass may be best determined by CT imaging. Nutritional endpoints and measures of metabolism can be quite complex. However, change in appetite and body weight remain extremely useful measures of clinical benefit. The most controversial area relates to assessment of physical function. While stair climb power, 6-minute walk, hand grip strength and other measures have been used in clinical trials, none of them have shown consistent benefit that correlates with change in LBM. While we have much to learn about the inter-relationship between muscle mass and muscle function, improvement in physical function may be best measured by patient reported outcomes. Ongoing and future clinical trials in cancer cachexia should assess all 3 domains, which will improve our understanding of this syndrome and ultimately lead to better treatment options for our patients.