Breakthrough supportive care: Overcoming cancer anorexia/cachexia

Up to 70% of patients with advanced cancer, including those with advanced non-small cell lung cancer (NSCLC), experience cancer anorexia/cachexia syndrome, a condition characterized by decreased appetite and food intake and loss of body weight including both lean body mass (LBM) and fat mass.^1,2 By definition, cancer anorexia/cachexia syndrome cannot be reversed with nutritional support alone.3 This debilitating syndrome, also known as wasting syndrome, is associated with decreased quality of life, lower tolerance to chemotherapy, reduced physical functioning, and worse survival.^4,5 Despite the great need, there are few therapeutic options and no standard of care for the treatment of cancer anorexia/cachexia, other than treating the underlying disease.

Current treatment options primarily consist of megestrol acetate, a synthetic derivative of progesterone administered to improve appetite; and dexamethasone, a corticosteroid that increases fat mass. Unfortunately, these drugs often lead to decreased muscle mass and additional serious side effects including thromboembolic events, adrenal insufficiency, blood clots, and loss of muscle over time.^6-12 Whereas oncology nurses often supplement pharmacologic therapy with nutritional counseling to increase food intake in patients with advanced cancer, this type of intervention rarely results in increased body weight and muscle mass. Consequently, conventional wisdom within the oncology community was that cancer-related anorexia/cachexia could not be addressed without curing­—or altering the manifestation of—the patient’s underlying cancer.

RATIONALE FOR PHARMACOLOGIC INTERVENTION

In the quest to identify and develop a safe and effective treatment for anorexia and cachexia, researchers have focused increasing attention in recent decades on ghrelin, the so-called hunger hormone. Ghrelin is the natural ligand for the ghrelin receptor which, when activated, has appetite-stimulating and anabolic effects¹³; effects that have been known for at least the last 15 years. The challenge has been to discover and develop a ghrelin receptor agonist that is both effective and well tolerated.¹⁴ That challenge appears to have been met by anamorelin HCl, an orally active, highly selective ghrelin receptor agonist.¹⁵ Now in phase III of clinical development, accumulated data suggest that anamorelin provides three key benefits long sought by patients with cancer-related anorexia/cachexia and the physicians who treat them: increased appetite, increased LBM, and increased fat mass. Whereas currently available therapies offer one or two of these benefits, anamorelin may be the first to deliver on all three.