Course Authors
Robert M. Russell, M.D., and Joel Mason, M.D.
In the last three years, Dr. Russell has received grant/research support from BASF and Roche Vitamins. Dr. Russell has also served as a consultant for Whitehall Robbins-Quaker; Dr. Mason has received grant/research support from Mead-Johnson Nutritional and also served as a consultant for Mead-Johnson Nutritional.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Discuss the nutritional and clinical outcomes to be expected with the use of appetite stimulants
Describe how nutritional vehicles with 'targeted' nutrients might provide clinical benefits to the cancer patient
List some of the alternative/complementary nutritional therapies that cancer patients frequently self-medicate themselves with.
Russell
How do we treat a malnourished patient with cancer? There are several modalities that have been used including appetite stimulants, prokinetic agents and immunomodulatory agents. Can you discuss each and provide the evidence as to the effectiveness or ineffectiveness of these treatment modalities? Let's begin with appetite stimulants.
Appetitite Stimulants
Mason
The response to these medications is highly variable and I've found that a minority of patients responds in an excellent fashion. In the majority, there's only a modest effect. Nevertheless, one can't predict which patients are going to be the responders.
In some patients, mere stimulation of the appetite can lead to a significant increase in oral intake. The most widely studied agents in this regard are progestational agents such as megestrol acetate, which is the agent used in the United States, and a related compound called medroxy progesterone acetate, which is used primarily in Europe. Both of these agents have been shown to increase significantly appetite and dietary intake among cancer patients. However, several qualifications must be mentioned in terms of their efficacy.
First, it takes several weeks for these agents to reach their full effect. With both agents, it is not unusual to see a four- to six-week lag between the onset of therapy and the time the patient reaches maximal increase in appetite. Second, there continues to be a considerable argument as to whether the weight gain is of any benefit. Studies demonstrate that the majority of the weight gain is in adipose tissue, a smaller amount is extracellular fluid, and it is controversial as to whether there is any substantial increase in lean body mass amongst these patients.(1) A not insignificant positive effect of these agents among cancer patients is a consistent improvement in the "sense of well-being" that is frequently reported.
I'd like to make a brief comment about the dose required for efficacy. With the use of megestrol, the studies demonstrate that an increase in effect is seen as one increases the dose to 800 mg per day.(2) Beyond that, there seems to be no further positive effect. In regard to side-effects: this class of drugs falls in a category that is thought to increase thromboembolic events and, therefore, they are relatively contraindicated in patients who have sustained prior thromboembolic events. Nevertheless, the increased risk must be rather small, since the studies demonstrate no greater rate of such events compared to the placebo groups.
Other appetite-stimulating agents have been investigated. The cannabinoids are most frequently discussed. Trials using the oral form of cannabis do tend to show a decrease in nausea, particularly that induced by chemotherapy and a significant appetite stimulating effect, but they have not been shown to effect a significant weight gain in any kind of convincing fashion.
In some situations, nausea and/or loss of appetite result from poor gastrointestinal motility and in these situations, a prokinetic agent, such as metaclopamide or domperidone, can be used. These agents are most scientifically administered when dysmotility has been documented by a gastric emptying study or some other means, although sometimes an empiric therapeutic trial is reasonable. At the time of this discussion, a very effective agent, cisapride, has, unfortunately, been taken off the market because of rare, but nevertheless fatal, induction of arrhythmias.
Immuno-modulating Agents
Russell
Joel, can you also review the data on immuno-stimulating or immuno-modulating agents?
Mason
Not only do these liquid nutritional formulas perform the function of providing all of the nutrients that a patient needs, but they also have "targeted" nutrients in pharmacologic quantities that are said to have effects beyond their nutritional value alone. The formulas that have caught the most attention are the so-called immuno-modulatory agents. These contain supplemental levels of omega-3 fatty acids, argenine, RNA and glutamine, all of which are said to positively modulate the immune system and thereby improve the cancer patient's resistance to significant infection and other insults to the immune system.
Although I must admit that I initially had considerable skepticism in regard to these formulas, there have now been several large prospective randomized trials which indicate that malnourished cancer patients who are about to undergo surgery do better when their nutritional status is restituted with these formulas compared to either a conventional enteral formula or TPN.(3),(4) It is important to emphasize that these trials have only been positive when use of these formulas had begun before surgery or within 48 hours after surgery. Significant decreases in infections have been reproducibly observed in these trials.
Two recent meta-analyses support these conclusions.(5),(6) One large trial of 195 subjects is often quoted since it did not demonstrate any beneficial effect of these agents. But I should point out that the individuals in this trial were exceptionally well nourished -- their mean weight loss was less than five percent and their mean serum albumin was in the normal range. Therefore, it's not surprising that patients in this particular trial didn't see any benefit from the immuno-modulatory formula.
Russell
Another problem that has been treated nutritionally is that of mucositis secondary to chemotherapy and radiotherapy. Can you tell us which nutrients might be useful in these conditions?
Mason
Several small trials with both topical vitamin E, as well as glutamine solutions, have looked at the efficacy of immuno-modulators in the treatment of oral mucositis induced by radiation and/or chemotherapy. Data from these rather small trials have been promising to date but the efficacy has not been tested on a large scale and, therefore, no definitive claim with respect to efficacy can be made.
Alternative Treatments
Russell
Whether or not physicians like it, many patients with cancer seek alternative modalities of treatment that they may be taking along with the more conventional modes of treatment 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 the diagnosis was established.(7) This, usually, is in addition to their conventional treatment. What evidence is there that some of these alternative treatments may hold promise?
Mason
Rob, almost by definition, an alternative therapy has not been definitively shown to be effective because once it's been shown to be effective it transforms itself into mainline therapy. Some agents and diets that patients will use include: bromelain, green tea, shark cartilage, laetrile, macrobiotic diet, Gerson diet and Livingstone therapy. Of these, only green tea has shown some efficacy against cancers in the setting of prospective randomized clinical trials and even that data is tentative.(8),(9)
Despite the lack of proven efficacy, it still behooves the physician to insure that they are aware of all of the alternative therapies that the patient is subjecting themselves to because of potential side effects and drug interactions with the agents that the conventional physician is administering to the patient. For instance, it is now widely known that some of the herbal agents in Chinese herbal mixtures can have significant autonomic stimulation of the heart. An example from the past is the use of laetril, which induced cyanide toxicity in some patients.
It is also important for the physician to remind the patient that there is little consistency in preparation, particularly amongst the admixtures of herbs that are seen in some of the Chinese herbal concoctions. This makes it difficult both on the physician as well as the patient, and makes it particularly difficult on the medical researcher who wishes to study the efficacy of these agents.
Russell
Joel, could you summarize some of the practical conclusions for the readers of this Cyberounds®.
Take Away Summary
Mason
Rob, I think the following points are the salient ones:
- Wasting, a form of protein calorie malnutrition that involves the loss of weight and lean mass, is common in cancer patients, particularly those with gastrointestinal, hepatobiliary and head and neck cancers. It carries with it negative consequences in regard to morbid events, the ability to withstand therapy and survival. An unintentional loss of greater than or 10% of the usual body weight constitutes a convenient and surprisingly accurate means of identifying those patients whose malnutrition is moderate to severe.
- Routine identification of those cancer patients with moderate to severe malnutrition is important because it is these patients who will most clearly benefit from aggressive nutritional support in the preoperative setting, and during chemotherapy and radiation. It is, nevertheless, worthwhile to provide aggressive nutritional support to well or mildly malnourished patients if it's projected that they will fall far short of meeting their nutritional needs for a period of more than seven days. An oral or enteral approach to aggressive nutritional support is more physiologic than a parenteral approach, less expensive and appears to be fraught with fewer instances of serious morbidity.
- All cancer patients undergoing allogenic bone marrow transplantation appear to benefit from prophylactic aggressive nutritional support. TPN has most often been used in this setting. There is some evidence that when a parenteral approach is taken, supplementing the TPN with glutamine conveys nutritional and immunologic benefits that translate into fewer infections and shorter hospitalization.
- When aggressive nutritional support is undertaken in malnourished cancer patients undergoing major surgery, further gains may be realized by using "immunoenhancing" enteral formulas in the pre- and immediate post-operative period instead of conventional tube feeds or TPN.
- A very large proportion of patients with these cancers will use alternative medical treatments in conjunction with conventional treatments and often do not mention such treatments unless specifically requested to do so. Thorough and sensible management of the patient dictates an awareness of all of the treatments that are being used.