Therapy Insight: Cancer Anorexia−Cachexia Syndrome-When All You Can Eat Is Yourself

Alessandro Laviano; Michael M Meguid; Akio Inui; Maurizio Muscaritoli; Filippo Rossi-Fanelli

Disclosures

Nat Clin Pract Oncol. 2005;2(3):158-165. 

In This Article

Summary and Introduction

Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia−cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass—and to a lesser extent adipose tissue—occurring even before weight loss becomes apparent. Cancer anorexia−cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic−cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

In recent years, our cumulative understanding of a number of scientific breakthroughs in the fields of tumor biology and genomics has translated into novel antineoplastic therapeutic approaches. Thus, the use of radiotherapy and chemotherapy is now complemented by gene-driven therapy that will yield improved response rates and prolonged survival, particularly in patients whose cancers are not susceptible to eradication.[1] Although many tumors can be treated, only a few patients with metastatic cancer are likely to be cured. Consequently, supportive care is a critical issue in the management of cancer patients, wherein oncologists positively influence not only survival, but quality of life and nutritional status.

The presence of a tumor can be clinically suspected when patients report anorexia accompanied by marked weight loss; both symptoms that frequently lead patients to seek medical advice. While anorexia is defined as the loss of the desire to eat, which frequently leads to reduced food intake, cachexia is characterized by profound loss (up to 80%) of both adipose tissue and skeletal muscle mass that eventually leads to hypoalbuminemia and asthenia, which, together with anemia, a frequent comorbidity in cancer patients, limit physical activity and consequently inhibit protein synthesis.[2] The weight loss caused by cancer differs from that observed during starvation, which is characterized by preservation of lean body mass. In contrast, both adipose tissue and, in particular, lean body mass are markedly depleted during cachexia.[2] Furthermore, in many cancer patients, particularly those with pancreatic or lung cancer, resting energy expenditure is not suppressed by progressive weight loss, but can even be increased, thus exacerbating the detrimental effects of wasting and reduced food intake on nutritional status.[2]

In cancer patients, anorexia and cachexia can co-exist, although the degree of weight loss cannot be ascribed completely to reduced food intake. Indeed, the muscle wasting observed in cancer patients occurs even in the presence of a normal food intake, and increased muscle proteolysis is detectable even before weight loss occurs.[3] Consequently, in cachectic cancer patients, the mere provision of nutrients via artificial nutrition is not effective in preventing muscle wasting or restoring lean body mass.[4] Anorexia per se reduces food intake and promotes weight loss, but when it accompanies cachexia it acts synergistically to impact on patients' morbidity, mortality and quality of life. To paraphrase the clinical consequences of this deadly combination, all that anorectic−cachectic patients can eat is themselves.

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