Anorexia in cancer patients: A syndrome

Multi-drug therapy appears to be better than a standard single drug in treating anorexia, says Mellar P. Davis, MD, FCCP, of the Cleveland Clinic.

Anorexia is a syndrome characterized by loss of appetite, satiety, mixed satiety and loss of appetite, altered food preferences, changes in taste and smell, lack of reward or pleasure from eating and diurnal variations in intake. His research found that among cancer patients with anorexia:

-- 62% had diurnal appetite changes

-- 57% had food aversions (56% chicken, beef, fish)

-- 68% had taste changes (this correlated with age)

-- 40% experienced changes in smell: Some developed nausea when food was brought into a room, or they couldn’t smell or they had a hypersensitivity to smell.

“The interesting thing is that there is a lack of rewarding effect in about 25% of patients,” Davis says. “If you ask them ‘if you never had a tray brought into your room again, would that bother you?’ About a quarter of the patients would say no.”

There is another variation when people get hungry. The general population tends to feel hungrier and eat more at night. There tends to be an inversion of this with cancer patients as they are able to eat more in the morning, Davis says. The Cleveland Clinic study found that at least in advanced cancer patients, there was an anorexia-cachexia cluster.

“You would anticipate that you would have weight loss with anorexia, but there are also gastro-intestinal symptoms and fatigue clustered to anorexia. We didn’t find any association with neuro-psychiatric or sleep disorders so this seems to be more organic-related, at least in our population.”

There are multidimensional questionnaires for assessing anorexia. One of the most common is the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) with 12-18 questions. Also used is the Bristol-Myers Anorexia/Cachexia Recovery Instrument (BACRI) with nine questions. The multidimensional scales are reliable and valid and responsive to change over time, but may be inadequate to assess the full experience and pick up the taste and smell changes over time, Davis says, so there really isn’t a comprehensive anorexia instrument.

The Cleveland researchers studied whether a simplified questionnaire could be substituted for a multidimensional scale in trials so they combined a numerical rating scale and a categorical scale (mild, moderate and severe) and compared it with Anorexia Cachexia Subscale (AC/S 12). They found a moderate correlation, but over time AC/S 12 was a better predictor of survival, and therefore a good instrument to use in trials.

Current treatments include the orexigens (appetite stimulants) dexamethasone, megestrol acetate, dronabinol, mirtazapine, melatonin, omega 3-FA, and thalidomide; all have varying degrees of success.

Smith said one of the most “practice changing” recent studies he has seen is the Navari and Brenner randomized study in 2009 for the treatment of cancer-related anorexia with olanzapine and megestrol acetate. Olanzapine (OLN) is an FDA-approved antipsychotic that blocks multiple neurotransmitters. Treatment was oral MA at a dose of 800 mg. a day or oral MA plus oral OLN at a modest 5 mg/day.

Results were much better for the combination of megestrol and olanzapine than for just the megestrol and resulted in significantly more weight gain, improved appetite, reduced nausea and improved quality of life. In other multi-drug trials, polyphenol diet plus megestrol acetate, omega 3-FA, levocarnitine and thalidomide was better than single-drug therapy. And with a polyphenol diet, megestrol acetate and celecoxib was safe and produced a positive response in 22 of 39 patients.

“You won’t find a single drug that will reverse anorexia,” Smith said. “We will need multi-agent therapies.”