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Dr West

Loss of Appetite and Weight Loss: A Very Common and Difficult Problem for Cancer Patients

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Loss of appetite and the weight loss that accompanies it are very common problems, seen in up to 80% of patients with advanced cancers, and this issue certainly appears as an issue on the discussion boards. In many cases, it’s one issue on a list of problems, and indeed we’ve gone far too long without a good discussion of this topic that deserves some attention.

A more formal definition of what we see so frequently in the clinic is “anorexia-cachexia syndrome” (ACS). In oncology terms, anorexia just means “loss of appetite”, not the psychiatric focus on being overweight (anorexia nervosa), and cachexia (pronounced “ka-KEK-see-ah”) is a significant concerning weight loss. The ACS syndrome is typically defined as a loss of 5% of the pre-illness weight over a 2-6 month period, but the term “cachectic” is a term health care workers generally use to describe someone who is quite underweight. As you might suspect, the ACS syndrome that also includes nausea, early satiety (feeling full), and fatigue is associated with a shorter survival than is seen in people who eat better and maintain their weight.

Incidentally, this is one of the reasons I and some other oncologists aren’t fans of strict diets and extreme avoidance of sugar. Seeing so many patients in a spiral of weight loss that is difficult to manage, so I’m certainly wary of patients losing much weight even voluntary – it often comes all too easily.

ACS is actually divided into a primary form, which is weight loss caused by a metabolic syndrome directly by the cancer, and a secondary form that is weight loss caused by barriers like nausea, mouth sores, esophagitis, taste changes related to chemotherapy, and other indirect causes of decreased food intake. The rest of this post will discuss primary ACS.

The underlying cause(s) of primary ACS are complex and not entirely understood. It entails increased metabolic rates and decreased muscle mass. Patients with primary ACS have high levels of proteins called “acute phase reactants” that are generated in times of stress, inflammation, and general illness. The cancer itself releases many of the destructive proteins, with names like “tumor necrosis factor”, that stimulate inflammatory pathways. The body breaks down proteins faster than usual (there is always a normal about of protein destruction and building/rebuilding in ongoing, daily cell maintenance), and it produces lower levels of new proteins. This leads to an overall higher metabolic rate than is ideal for their body weight, and the net result is a loss of protein and muscle mass over time.

How is it treated? Historically, people have tried to push food into people, but studies have actually shown that in patients with primary ACS, nutritional support doesn’t translate to improvement in body mass. This is because the body still continues to break down proteins in the face of higher caloric intake. But nutritional support, whether in the form of concentrated high calorie and high nutrition food like Boost or Ensure, or tube feedings directly into the stomach, or even IV nutrition, can be helpful for patients with secondary ACS. This is because secondary ACS isn’t accompanied by the metabolic spiral that nullifies the benefits of nutritional support.
Despite the complexity of the interaction between improved nutrition and body mass in ACS, our primary treatments for ACS have targeted improvement in appetite stimulation. One reason is that weight loss isn’t the only manifestation of ACS: patients and family members often find it upsetting for a patient to not be able to participate in meals, and not eating is a regular reminder several times per day of the effects of the cancer.

One of the most commonly used treatments for primary ACS is a hormonal treatment in the class called progestins: typically megestrol acetate, or Megace. There are certainly studies that show weight gain with megace in patients with cancer, but this is more in fat than muscle/lean body mass. Some studies have used daily doses of just 180 mg, which can be enough to increase appetite, oral intake, and weight, it’s more common to give higher doses in the range of 480-800 mg/day. I often give a concentrated version called megace ES (for extra strength), which is typically dosed at 625 mg as one tablespoon per day, but it’s several hundred dollars per month, which is higher than other forms that are also on the expensive side. Another concern with megace or other progestins is that they can increase the risk of blood clots, which are already pretty common in patients with cancer (about 4-6 times the frequency in patients without cancer). In these situations, though, you often need to weigh the fact that a patient is experiencing now against the possibility of a new problem in the future. Risk of blood clots is certainly something I discuss with patients, but in many cases we decide that it’s more important to focus on current problems than potential issues down the road.

Another relatively common treatment for diminished appetite is steroids like decadron or prednisone, and they can also improve energy and overall well being, but studies haven’t shown significant improvements in weight. They have an advantage in being inexpensive, and some patients need to be on them for other reasons (such as edema in some patients with brain metastases), but side effects can be a real problem, particularly with longer-term use, when patients can become significantly immunocompromised. They can certainly be helpful for a few weeks at a time. A typical daily dose would be about 2 mg of decadron or up to about 20 mg of prednisone.

A useful byproduct of the side effect of “munchies” associated with marijuana, appetite stimulation is now exploited as a benefit of marinol (dronabinol) (typical dose 2.5 – 10 mg twice daily before lunch and dinner), which includes the active ingredient THC. Marinol has been extensively used and tested in AIDS-related weight loss, and it does increase appetite; it hasn’t been convincingly shown to significantly increase weight. It also hasn’t appeared as effective in patients with cancer, but it can help patients with nausea and malaise leading to secondary ACS.

All of the above interventions focus on increasing appetite and food intake, and they haven’t been overwhelmingly, consistently helpful in improving weight in cancer patients, or certainly a more pivotal endpoint like survival. This is understandable when we remind ourselves that caloric intake is only part of the negative spiral in ACS. Newer treatments are focusing directly on breaking the cycle of hormonal and cytokine effects that lead to the cascade of detrimental metabolic effects in cancer patients, but this work is still in early studies. Our hope is that research directed against TNF and other mediators of the broad metabolic syndrome seen so commonly in patients with progressing cancer will yield interventions more effective than our current approaches. Unfortunately, ACS is a complex problem that evades simple fixes of just getting more food into someone.

12 Responses to Loss of Appetite and Weight Loss: A Very Common and Difficult Problem for Cancer Patients

  • Dr Pennell
    Dr Pennell says:

    Great summary of a major problem in advanced cancer patients. The ACS, while secondary to the cancer, can be a direct contributor to the eventual death of the patient with widespread disease but no tumor location that is imminently fatal (such as widespread bony lesions). It would make a huge impact on quality of life if this could be addressed.

    There are some interesting drugs in development for this problem, one promising class of which are the ghrelin analogs (i.e. anomorelin), which stimulate growth hormone and insulin like growth factor (IGF-1) secretion. In early phase trials (healthy subjects) these stimulated appetite, weight gain, and more importantly, increased lean body mass rather than fat. Anamorelin is currently being tested in lung cancer patients, with Jennifer Temel at MGH as the national PI of the trial.

    I wanted to also add one more drug to the list of possibilities. I have used Remeron with some modest success, which is an older antidepressant that has weight gain as a side effect. It can be useful in someone who is depressed and anorexic, but I am not aware of controlled data in cancer patients using this drug.

  • rlei says:

    Do you have any specific recommendations for pts who have an OK appetite (with or without Megace) that continue to lose weight?

  • Dr Harman says:

    Megace has the most evidence for increasing weight in cancer patients. This is definitely the tougher part of ACS, as there are more medications that improve appetite without increasing weight. Remeron (mirtazapine), the anti-depressant mentioned by Dr. Pennell, has weight gain well-documented as a side effect, but I too am not aware of studies of this medication for weight gain in ACS.

    -Dr. Harman

  • reginac says:

    For me, the problem is that I no longer feel hungry. The only reminder I have to eat is when I start to feel dizzy or woozy. Part of my problem is that I have a constricted esophagus which was dilated to 54 french this month, but I am still experiencing regurgitation especially when I eat dry foods. Is there anything out there aside from Dronabinol that can help with this?

  • Dr West
    Dr West says:

    I’m sorry to say taht I don’t know of any specific recommendation and would be inclined to ask a gastroenterologist for thoughts.

    Hope things are going OK otherwise.

    -Dr. West

  • certain spring says:

    Really sorry to hear you have this going on, Regina. Might it be worth posting in the forums to see if anyone has experience that can help – of oesophagal cancer for example? I was going to suggest Marinol but I now realise that’s Dronabinol by another name. Hope the dilation will ease things for you. And perhaps set an alarm clock for mealtimes, silly as it sounds? Very best.

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  • ajd7 says:

    My mother age 80 has stomach cancer and recently her tumor has grown causing her to have a full filling and loss of appetite. I read that D-Ribose and MSM with vitamin C may help. What are your thoughts.

  • Dr West
    Dr West says:

    Unfortunately, I don’t think these interventions are very likely to be effective in the face of a stomach cancer taking up much of the space in the stomach.

    I’m very sorry she and you are facing this.

    -Dr. West

  • yniloc says:

    My father has had lung cancer and recently got all of his right side removed. The reason we found the cancer is by chance, after he got admitted to the ER for liver inflammation, they caught the cancer in an Xray. His problem is that from the time that they caught the cancer (back in August) till now, his appetite has not improved. To add to this, he hasn’t been getting a good night’s sleep (an average of 2 hours). He is currently in the hospital again due to an infection, where they found some fluid in the area where his right lung was. My question is, can we do anything about the appetite? We have been trying to get him smaller, more frequent meals with no success. He has lost about 60 pounds since August and his PCP, oncologist, and thoracic surgeon all refuse to give him medication to increase his appetite.

  • yniloc says:

    He also is diabetic, has hypertension, and is 71 years old. They have put him additionally on warfarin.

  • Dr West
    Dr West says:


    This post was a discussion of the general approaches most commonly employed. It may be helpful to have him see a palliative care specialist about cancer-related symptoms, as they are often among the most proactive people with regard to these issues.

    Good luck.

    -Dr. West

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