Cancer-related anorexia/weight-loss syndrome, commonly experienced by patients with advanced incurable cancer, is characterized by general weight loss and muscle wasting, loss of appetite, overall decline in quality of life, and shortened survival. Most patients with advanced cancer develop this syndrome at some point during the course of their disease.

The approach to managing patients with cancer anorexia/weight-loss syndrome has improved dramatically over the past 50 years. A 1955 article described efforts to force-feed a cohort of 64 “terminal cancer patients” with various advanced malignancies, including cancer of the cervix, colon, stomach, pancreas, and breast. Study participants were subjected to nasogastric tube feedings. The investigators described how “many who were bedfast in the hospital were temporarily restored to family living without special care.” Even so, the investigators were not able to determine whether the patients' length of life was extended or shortened, further noting that “tumors that were palpable or visible seemed to increase in size…” Today, force-feeding patients with advanced, incurable cancer is viewed as ineffective and is almost obsolete. Despite progress in the management of cancer-related anorexia/weight-loss syndrome, however, many aspects of this syndrome continue to be vexing from a clinical and research perspective.

This chapter outlines areas of progress and ongoing challenge. We address: (1) the clinical significance of cancer anorexia/weight-loss syndrome; (2) the current thinking on its pathophysiology; (3) current treatment approaches; and (4) recent inconsistencies between translational and clinical research, all of which underscore the need for avid, continued clinical investigation.

Introduction

Over 50% of patients with advanced cancer suffer from loss of weight and/or appetite during the course of their disease. In a landmark Eastern Cooperative Oncology Group study, Dewys and colleagues found that loss of more than 5% of premorbid weight predicted a poor prognosis, independent of tumor stage, tumor histology, and patient performance status. This weight loss was also associated with a trend towards lower chemotherapy response rates.

How might we explain this prognostic impact? Investigators have hypothesized that loss of lean tissue is directly tied to prognosis. Because lean tissue carries all the body's metabolic machinery, these investigators have suggested there might be a cause and effect relationship between loss of lean tissue and an early demise. In fact, an excessive loss of lean tissue is a hallmark of cancer-associated weight loss. Although weight-losing cancer patients manifest loss of both fat and lean tissue, it is the loss of lean tissue that is the most dramatic and stands in stark contrast to the preferential loss of fat tissue observed in classical starvation. Thus, it may be hypothesized that a reversal of loss of lean tissue might improve prognosis. To date, however, despite ongoing investigation with such agents as eicosapentaenoic acid, thalidomide, adenosine triphosphate, anticytokine therapy, and nonsteroidal anti-inflammatory agents, this hypothesis remains unproved.

Independent of lean tissue wasting, however, a strong argument can be made for diagnosing and palliating anorexia. Wolfe and others interviewed parents of deceased children who died of cancer.