A two-part dialogue between Robert M. Russell, M.D., and Joel Mason, M.D.
Part I: The Problem
Malnutrition is a very common problem for hospitalized patients in general but it happens most to those who have been sick for a long time with chronic diseases such as cancer. What can you tell us about malnutrition among cancer patients?
Malnutrition is definitely a problem for cancer patients, but it is difficult to give a precise answer to your question because it depends upon how you define malnutrition. I can tell you, for instance, that one very large survey of several thousand patients who were about to begin chemotherapy for cancer found that about one-sixth had recently lost 10% or more of their normal body weight.
I focus on this particular statistic because exceeding this degree of weight loss (i.e., greater than 10% loss of normal body weight) has been shown to be the point at which overall health starts to decline. Statistically, it is also the threshhold at which patients' survival rates from surgery begin to decline markedly.
There are a lot of factors that determine which individual cancer patients will sustain weight loss, and how much. The type of cancer is one. For instance, in the same survey I mentioned above, only about 6% of patients with leukemia, sarcomas and breast cancer suffered weight loss of 10% or more, whereas 15 to 40% of those with gastrointestinal cancers had significant malnutrition. For obvious reasons, head and neck cancers are the most frequently associated with malnutrition; in several surveys more than 40% of head and neck cancer patients were malnourished.
Is there any evidence that malnutrition has a real impact on cancer treatment or on a person's chances of surviving the disease?
That's an excellent question and one that is frequently asked. Numerous studies strongly suggest that substantial malnutrition (such as the 10% standard) has serious consequences for cancer patients. Malnutrition reduces the effectiveness of chemotherapy, lowers overall quality of life and lowers patients' chances of survival. Perhaps the strongest evidence, though, is that, overall, the success rates of cancer treatments are significantly better when patients' nutritional problems are dealt with.
Causes of Malnutrition
There are many causes of malnourishment, including pain, depression and the side effects of chemotherapy or radiation treatment. What are the most important factors that can lead to malnutrition — or that can predict malnutrition?
That's a rather complex issue because in most cancer patients, weight loss has more than one cause. In order to adequately address the issue of malnutrition in a cancer patient, it is a good idea to start by identifying the cause or causes.
The simplest and most obvious cause is insufficient dietary intake, usually caused by loss of appetite. Loss of appetite is very common among cancer patients, whether caused by emotional depression or by a loss of interest in food after the nausea and vomiting caused by certain cancer treatments. One cause that is sometimes overlooked is problems with the swallowing mechanism. This is extremely common in head and neck cancers, whether from the tumor itself or as a result of the surgery or radiotherapy that is used to treat the tumor.
Cancer and Metabolism
Could you tell us how cancer can alter a patient's metabolism?
Cancer can cause great changes in how the body metabolizes protein, carbohydrates, and fat. This in itself can be a major cause of weight loss.
These metabolic changes work together in ways we still don't quite understand to cause very large reductions in lean body mass, mostly muscle, with much smaller decreases in fat. This is similar to what we see in acutely ill, hospitalized patients and is probably caused by many of the same factors. Because more than 95% of the body's metabolic activity occurs within the lean body mass, loss of lean body mass can have a drastic impact both on the effectiveness of medical treatments and on general health.
What is the best way to assess nutruitional health in cancer patients? Do you use Body Mass Index (BMI)?
There are many high tech ways to do nutritional assessment, but some of the simplest approaches are just as effective. For instance, using the standard of unintentional loss of greater than 10 percent of the usual body weight can be very useful.
There are, however, cases where body weight is not the best method — in patients with cirrhosis, for example. In these patients, we frequently rely on a measure of skeletal muscle mass called the "creatinine-height index."
There is also something called the "prognostic nutritional index" that was developed approximately 20 years ago for cancer patients about to undergo major surgery. This does a reasonably good job of predicting whether malnutrition has reached the point of affecting survival rates.
Tube feeding and other aggressive techniques would seem to be an obvious solution to treating malnutrition in someone who is seriously ill and cannot or will not eat enough. Unfortunately, however, studies on aggressive nutritional support have been rather disappointing with regard to cancer treatment outcomes. Even worse, there is some evidence that in some cases aggressive nutritional support can feed the cancer and make things worse.
This brings us back to the question of assessment. Are there any situations where you believe that nutritional support is beneficial for cancer patients?
The answer to your question is a qualified yes, depending in part on individual circumstances, including how malnourished the person is.
There is good evidence that aggressive nutritional support can benefit cancer patients who are about to undergo major surgery. It is important to add that, according to the latest studies, only moderately to severely malnourished cancer patients with cancer who are about to undergo major surgery seem to benefit from aggressive nutritional support. It seems to make little difference for patients who are only slightly malnourished. I would also like to make it clear that we are talking about aggressive nutritional support that is given before an operation, not afterward.
How many days or weeks of nutritional support prior to surgery are we talking about?
The studies indicate that 8 to 10 days of preoperative nutritional support can make a difference in surgical outcomes. I'd like to underline that you will not see any significant weight gain or other obvious improvement during those 10 days.
Nevertheless, there is good evidence that enzyme systems and overall physiology are improved during those 10 days, and that this makes a difference. I'd like to further emphasize that nutritional support can be provided on an outpatient basis and does not necessarily have to take the form of tube feeding or some other high-tech approach. Sometimes, drinking nutritional supplements is sufficient.
The second situation where cancer patients can benefit from aggressive nutritional support is among patients who are about to begin chemotherapy or radiation therapy. While nutritional support can reverse malnutrition and improve general health, however, it does not seem to make the treatments themselves more effective.
The effects of aggressive nutritional support on patients undergoing radiation therapy have been most extensively studied in those with head and neck cancers because these patients tend to have swallowing problems and a high incidence of malnutrition. There is reasonable evidence that the use of what is called a percutaneous endoscopic gastrostemy tube (PEG) to deliver tube feedings during and after a course of radiation can prevent further malnutrition and significantly improve the quality of life, even if, statistically, it does not make any difference in treatment outcomes.
Another situation where aggressive nutritional support should be considered for cancer patients is for those who are facing a bone marrow transplant. For reasons that are not entirely clear, there is, even among well-nourished people, a benefit to using a feeding technique called total parenteral nutrition (TPN) during and after a marrow transplant. This may be because bone marrow transplantation is such a trauma for the entire the body and its effects are so long-lasting that without nutritional help, even well-nourished patients would lose significant amounts of weight during recovery. TPN seems to prevent this.
The studies show that using TPN during and immediately after the transplant also increases survival rates. TPN support normally continues for at least two weeks after the transplant.
So, in summary, aggressive nutritional support can help malnourished patients going into surgery as well as malnourished patients undergoing chemotherapy or radiation therapy. It also helps improve the outcome of bone marrow transplantation. Most of the benefit, however, comes not in the form of higher success rates for cancer treatments, but rather in the form of a better quality of life and better overall health.
Part II: The Treatment
What is the best way to treat a malnourished patient with cancer? There are several methods currently in use, including appetite stimulants and two classes of drugs called prokinetic agents and immunomodulatory agents. How effective are they? Let's begin with appetite stimulants.
These drugs help some people and not others. Unfortunately, the effect seems to be fairly random. That is, we can't really predict which patients are going to be helped.
For some people, mere stimulation of the appetite can lead to a significant increase in how much they eat. The most widely studied appetite stimulating drugs are megestrol acetate and a related compound called medroxy progesterone acetate. Both have been shown to significantly increase appetite and dietary intake among cancer patients. However, both have their drawbacks.
First, it takes several weeks for them to reach their full effect. It is not unusual to see a four- to six-week lag between the beginning of therapy and the time the patient's appetite bounces all the way back to normal. Second, there continues to be considerable debate among medical experts about the type of weight gain these drugs achieve. Studies have shown that most of the gain consists of fat and a smaller amount is fluid. It is debatable whether there is any substantial increase in lean body mass, which is the most desirable type of weight gain for cancer patients.13 On the positive side, many cancer patients do report an increased sense of well-being after taking these drugs.
Other appetite-stimulating drugs currently in use include cannabinoids (drugs derived from marijuana). They do seem to help reduce the nausea produced by chemotherapy, along with some appetite stimulating effects, but they have not been shown to be very effective in achieving significant weight gain.
Sometimes, nausea and loss of appetite result from poor gastrointestinal motility. In these cases, drugs called prokinetic agents, such as metaclopamide or domperidone, are used. Recently, a very effective prokinetic agent, cisapride, was taken off the market because in rare cases it caused fatal heart arrhythmias.
Joel, can you give us the latest word on immuno-stimulating or immuno-modulating agents?
These are liquid nutritional formulas that provide all of the nutrients that a patient needs, and also contain "targeted" nutrients that supposedly help the immune system. These include omega-3 fatty acids, argenine, RNA and glutamine, all of which are said to improve the cancer patient's resistance to infection and other insults to the immune system.
Although I must admit that I initially had considerable skepticism about these formulas, several large studies have shown that malnourished cancer patients who are about to undergo surgery do better on these formulas than on conventional formulas. Significant decreases in infections have also been observed in these studies.
Whether physicians like it or not, many people with cancer take alternative treatments on their own, often at the same time as conventional treatments such as radiotherapy and chemotherapy. In one study of patients with breast cancer, almost 11% had used alternative medicine before they were given the diagnosis of breast cancer, and 30% started using it after being diagnosed.
What evidence is there that some of these alternative treatments may actually work?
Rob, the effectiveness of alternative therapies is questionable almost by definition because once a treatment has been shown scientifically to be effective it normally becomes a mainstream treatment. Some popular alternative treatments include bromelain, green tea, shark cartilage, laetrile, macrobiotic diet, Gerson diet and Livingstone therapy. Of these, only green tea has been shown in studies to have some efficacy against cancers and even those results are tentative.
Despite the lack of scientific proof that alternative therapies work, physicians should be aware of whatever treatments their patients are using because of potential side effects and drug interactions. For instance, it is now widely known that some of the ingredients in Chinese herbal mixtures can stimulate the heart. An example from the past is the use of laetrile, which caused cyanide poisoning in some users.
It should also be remembered that there may be little consistency in the preparation of some alternative medicines, particularly with some of the Chinese herbal concoctions. This makes it difficult both to safely use and to study these treatments.
Joel, could you summarize your thoughts on this topic?
Rob, I think the following points are the key ones:
- Wasting, a form of malnutrition that involves the loss of lean mass, is common in cancer patients, particularly those with gastrointestinal, liver and head and neck cancers. Malnutrition can hurt these patients' ability to withstand therapy and to survive. An unintentional loss of greater than or 10% of normal body weight is a convenient and very accurate means of identifying those patients with serious malnutrition.
- It is important for anyone in this category to consider some form of aggressive nutritional support, whether before an operation or during chemotherapy and radiation.
- Cancer patients undergoing bone marrow transplantation should receive aggressive nutritional support. TPN is most often used. There is some evidence that adding a supplement such as glutamine helps boost the immune system; this translates into fewer infections and shorter hospitalizations.
- When aggressive nutritional support is given to malnourished cancer patients undergoing major surgery, "immunoenhancing" formulas appear to be an improvement over conventional tube feeding or TPN formulas.
- Today, a very large proportion of people with cancer will use alternative medical treatments in conjunction with conventional treatments. Sensing disapproval or skepticism, they often do not tell their doctor about these treatments unless specifically asked. Regardless of whether or not these treatments are scientifically proven to be effective, you should make sure your doctor knows — and doctors should make sure they find out — about every drug or other treatment you or a loved one may be taking.