Cancer anorexia/cachexia syndrome can be a major problem for patients with advanced cancer, one that can have significant consequences in terms of how patients perceive their own health and well-being, and affects many of their caregivers. The syndrome dramatically impacts quality of life for patients as well as for caregivers, for whom it can be profoundly distressing to see an appetite-deficient patient refrain from eating while continuing to lose weight.

Currently available pharmacologic treatment options are of limited use in patients with cancer-related anorexia/cachexia, as they provide only short-term benefits and a significant profile of potential harms. Dexamethasone has been shown to induce hyperglycemia, diabetes, and proximal myopathy, and is associated with psychotropic effects ranging from profound depression and suicidality to hypomania. Patients on dexamethasone therapy may also undergo physical changes including weight gain often with the emergence of a moon face, buffalo hump, and striae commonly associated with glucocorticoids. In addition, dexamethasone is suitable only for short-term use, as long-term treatment may accelerate loss of LBM and loss of bone mineralization—an effect that is directly at odds with treatment goals in this patient population.6-8

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With megestrol, the rate of psychotropic effects is lower than with dexamethasone, but these effects do occur. More concerning is the fact that megestrol can induce deep vein thrombosis and pulmonary embolus in a population already more prone to these complications because of their cancer.9-12 Few would argue that such complications are acceptable side effects of a treatment that only stimulates appetite and does not address the underlying changes in LBM in patients with anorexia/cachexia.

The limitations of current treatment options thus make ghrelin receptor agonists a potentially promising mode of therapy. These agents may represent a new generation of treatments for cancer-related anorexia/cachexia, a class that may open up a wider range of options for patients who are considered untreatable or marginally treatable with currently available therapies. The ROMANA studies demonstrate that anamorelin safely increases LBM and total body weight while also improving anorexia/cachexia symptoms in a manner not seen with the current mainstays of therapy: megestrol and dexamethasone. Moreover, the benefits of anamorelin therapy appear early—within the first 3 weeks—and are sustained over time. Although hyperglycemia was observed in a small number of anamorelin-treated participants in the ROMANA trials, frank diabetes was rare. In addition, the rates of anamorelin-related hyperglycemia and diabetes in the ROMANA studies were far lower than those reported with dexamethasone, and were observed later in the course of therapy than is typical with dexamethasone.

If the anabolic effects of anamorelin prove to be a class effect of the ghrelin receptor agonists, these agents will likely attract increasing attention as they are studied further and brought into clinical practice. The hoped-for emergence of this new class of therapies for cancer-related anorexia/cachexia may thus be a boon to a patient population that has waited decades for a safe and effective treatment that provides meaningful, long-term benefits.

David Currow is professor of Palliative and Supportive Services, Flinders University, in Adelaide, SA, Australia; and director of Palliative Medicine and Hospice Care at Dartmouth-Hitchcock in Lebanon, New Hampshire. 


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