Addressing Cachexia for Cancer Patients (and Their Caregivers)

Kate M. O'Rourke

Disclosures

November 19, 2015

Last year, Alice Golden, a two-time cancer survivor living in Billings, Montana, was diagnosed with stage III anal cancer. During her treatment, she developed cachexia. Handling her loved ones' reaction to this disorder was extremely difficult.

"My husband loves the cooking shows, and if I went into the kitchen and a cooking show was on, he had to shut it off. I would get sick to my stomach just thinking of food," said Mrs Golden at the recent Palliative Care in Oncology Symposium. "My sister came from Virginia to help us. Between my husband and my sister, they were constantly saying, 'You have got to eat.' The thing I dreaded the most when I woke up in the morning was having to deal with the issue of food."

Her solution was to cut up her food and hide it in a napkin. "They were so happy that I was eating, and I was so happy that I didn't have to deal with them about my not eating," said Mrs Golden.

Treatment Options

At the Palliative Care in Oncology Symposium, Charles Loprinzi, MD, the Regis professor of breast cancer research at Mayo Clinic in Rochester, Minnesota, and other clinicians discussed the management of anorexia/cachexia. This complex metabolic syndrome, associated with a variety of diseases, is characterized by decreased appetite and food intake and loss of body weight. Diagnostic criteria include weight loss of more than 5% over the past 6 months (in the absence of simple starvation), ongoing weight loss of more than 2% in individuals with a body mass index less than 20 kg/m2, or evidence of sarcopenia with any degree of weight loss greater than 2%.[1] Anorexia/cachexia develops in up to 70% of patients with advanced cancer.[2]

Dr Loprinzi pointed out that there are no drugs approved by the US Food and Drug Administration for this disorder, but some drugs are used off label. Over the years, clinicians have tested a number of drugs for cachexia/anorexia, and many of these, such as hydrazine, metoclopramide, and pentoxifylline, have been shown to be ineffective.[3] A recent review noted that existing therapies for cachexia/anorexia include orexigenic appetite stimulants, combination therapy with diet modification and/or exercise, and novel pharmaceutical agents, such as megestrol acetate, medroxyprogesterone acetate, ghrelin, and omega-3-fatty acid.[4]

"Cyproheptadine is an antihistamine that helps a little bit but not very much. Megestrol acetate works to increase appetite, and there is a dose response as you go from 160 mg up to 800 mg per day," said Dr Loprinzi. "It is reasonable to use orexigenic medications, such as progestational agents, corticosteroids, or anamorelin—if it becomes clinically available—for cancer-related anorexia/cachexia."

At the symposium, Jennifer Temel, MD, assistant professor of medicine at Harvard Medical School and clinical director of thoracic oncology at Massachusetts General Hospital in Boston, presented results from two phase 3 clinical trials, ROMANA 1 and ROMANA 2, that support the use of anamorelin for cachexia.[5] The two studies randomly assigned patients with unresectable stage III or stage IV non-small cell lung cancer and anorexia/cachexia to receive anamorelin (n=653) or placebo (n=326). Patients who received anamorelin had an increase in body weight, whereas those who received placebo lost weight or maintained their weight over the 12 weeks of the study (Table).

"Anamorelin significantly increased lean body mass and body weight in patients with advanced NSCLC and cachexia vs placebo; however, there was no difference in hand grip strength in either trial," said Dr Temel. "Patients receiving anamorelin also experienced a significant improvement in their anorexia-cachexia–related symptoms. Importantly, the drug was well tolerated, with no evidence of excessive toxicity and similar survival between study arms."

Table. Outcomes From the ROMANA 1 and ROMANA 2 Trials

  ROMANA 1 ROMANA 2
  Placebo Anamorelin P Value Placebo Anamorelin P Value
Lean body mass, kg -0.44 1.10 <.001 -0.96 0.75 <.001
Hand grip strength, kg -1.45 -1.00 .45 -0.95 -1.15 .74
Body weight, kg 0.14 2.20 <.001 -0.57 0.95 <.001
Anorexia/cachexia scale 1.92 4.12 <.001 1.34 3.48 .002
Fatigue scale -1.91 0.26 .05 1.23 1.37 .86
Total body mass, kg 0.07 2.87 <.001 -0.59 2.04 <.001
Fat mass, kg -0.13 1.21 <.001 0.09 0.77 .01


Dr Loprinzi pointed out that no treatment for anorexia/cachexia has been found to improve survival. "A family may say, 'Mom is going to die if she doesn't eat,' and I say, 'Yes, you are right, but she is also going to die if she does eat.' We haven't had any proof in any of these studies that the drugs actually improve survival," he said. "Neither appetite stimulants nor total parenteral nutrition has been shown to improve either the quality or quantity of life, and there is no good evidence that these things improve performance status." This information, while hard to hear, can actually educate families and allow for better family dynamics.

 
Neither appetite stimulants nor total parenteral nutrition has been shown to improve either the quality or quantity of life, and there is no good evidence that these things improve performance status.
 

According to Dr Loprinzi, "It is not unreasonable to use an appetite stimulant in a patient if that is what the patient wants to do." Some patients who are anorexic from their terminal disease, however, may not be bothered by this symptom. In one study of 32 terminally ill patients, researchers evaluated hunger and thirst during the final six 6 of their disease course.[6] The study found that 63% never experienced hunger, and 34% had hunger only transiently at the beginning of the observation period; those who experienced hunger only needed small amounts of food for alleviation of symptoms. The researchers concluded that food and fluid administration beyond the specific requests of patients may play a minimal role in providing comfort to terminally ill patients. Another study showed that in many patients who expressed hunger during their terminal illness, symptoms tended to cease after only a few days of decreased intake.[7]

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