GI Symptoms in Advanced Cancer ‘Difficult to Treat’

CLEVELAND, Ohio—Nearly half of the symptoms associated with cancer are gastrointestinal (GI), including anorexia, weight loss, dry mouth, constipation, early satiety, nausea and vomiting, taste change, and dysphagia. Yet these symptoms are among the most difficult to treat because their pathophysiology is not well understood, available drugs are not always effective, and multiple symptoms may occur together, Kristine A. Nelson, MD, said at a symposium on palliative medicine held at the Cleveland Clinic Foundation.

Anorexia, defined as the loss of appetite, and weight loss are the most common presenting symptoms of cancer, said Dr. Nelson, of the Harry R. Horvitz Center for Palliative Medicine, Cleveland Clinic Foundation. Anorexia frequently progresses to cachexia, which is characterized by poor condition, metabolic abnormalities, and severe weight loss.

Anorexia-Cachexia Syndrome

Cancer anorexia-cachexia syndrome is one of the most common causes of death in cancer. For this reason, weight loss tends to predict survival.

Anorexia is a common side effect of chemotherapy, radiotherapy, and many drugs. Psychosocial factors, such as depression and anxiety, may contribute, and so can physical factors, ranging from pain to oral problems to metabolic derangements such as hypercalcemia. The pathophysiology of cancer anorexia-cachexia syndrome is not completely understood, but cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 are known to play important roles.

Whether to treat anorexia has been a matter of controversy, Dr. Nelson said. Some physicians believe that since anorexia is part of the natural history of advanced cancer, treating it is unnecessary. Dr. Nelson said she disagrees with that approach. Although it is part of the natural history of cancer, anorexia should be treated if it will improve the patient’s quality of life, she said.

Treating anorexic patients who want to eat will improve their quality of life, she said. However, patients who are unwilling to eat or who can’t swallow should not be treated. In some situations, the family is eager for the patient to eat even when the patient does not want to do so. This can be a “tricky issue” for the physician to navigate, Dr. Nelson said.

The cause of the anorexia should be evaluated. Some causes of anorexia, including pain, oral hygiene, nausea, vomiting, early satiety, and drug-induced anorexia, can be treated and reversed. Treating anorexia is unlikely to affect cachexia, she added.

Appetite-Stimulating Drugs

Anorexia can be treated with a number of appetite-stimulating drugs, including metoclopramide for early satiety and nausea/vomiting, megestrol acetate, corticosteroids, and dronabinol (Marinol). Corticosteroids also prompt an increased sense of well-being.

Megestrol acetate can be given to patients regardless of their tumor hormonal status. “The recommended dose is 800 mg daily, but we have found that some patients respond to doses as low as 40 mg by mouth, twice daily,” Dr. Nelson said. Contraindications to megestrol acetate are peripheral edema, congestive heart failure, and a history of deep-vein thrombosis.

Dronabinol is synthetic THC, the active ingredient of marijuana. Indications for dronabinol are nausea and anorexia. “It may also improve mood,” she said. Dronabinol is given at a dose of 2.5 mg by mouth, three times daily, 30 minutes after meals. In patients over age 65, Dr. Nelson recommends dosing only twice a day.

Dronabinol can stimulate the appetite without giving the patient a “high” feeling, she said. The dosage can be increased to 5 mg. Contraindications are confusion, cardiac arrhythmia, history of seizures, and, possibly, history of drug use.

Dr. Nelson recommended discouraging patients who ask for marijuana instead of dronabinol. There are significant differences between marijuana, which contains more than 400 substances, and dronabinol, which contains one pure substance. In addition, there is limited research on marijuana and abundant research on dronabinol.

In addition to drugs, nonpharma-cologic measures can be used to encourage eating, Dr. Nelson said. These include creating an appealing environment in which to eat (in bed is less than ideal), preparing attractive meals of favorite foods, and offering small frequent meals.

Nausea and vomiting are among the most common symptoms associated with advanced cancer, and mechanisms vary. Some neuropathways for nausea may cause vomiting in up to 70% of advanced cancer patients, Dr. Nelson said.

Certain populations of patients are more at risk for the nausea and vomiting associated with opioids, she said. These include patients with good pain control, women, younger patients, ambulatory patients, those beginning opioid treatment, those affected by motion sickness, women who experienced morning sickness during pregnancy, and individuals who have been heavy alcohol drinkers.

Nausea and vomiting result from stimulation of a complex reflex coordinated by the vomiting center, located in the medullar lateral reticular formation. Several responses in the body may activate the vomiting center.

When prescribing drugs to treat nausea and vomiting, it is important to try to determine which mechanism of action is stimulating the vomiting center, Dr. Nelson said. “Try to treat the cause of the problem,” she said. Nausea often requires higher doses of medication to control than vomiting, she added.

Cannabinoids and benzodiazepines are effective if nausea/vomiting is caused by the cerebral cortex and limbic system. Phenothiazines, butyrophenones, and metoclopramide are useful if it is caused by the chemoreceptor trigger zone. Meto-clopramide and serotonin receptor antagonists are useful for nausea/vomiting caused by visceral afferents. Antihistamines and anticholinergics work on the vomiting center directly. Drugs can be combined, but, in general, she recommended avoiding combining two agents that work on the same area of the body.

When administering medication for nausea/vomiting, titrate carefully and choose the appropriate route of administration. If the oral route results in more vomiting, try a subcutaneous or IV route, Dr. Nelson said. Use round-the-clock dosing, and monitor side effects.

Early satiety, defined as appetite satisfied by an unusually small amount of food, is frequently confused with anorexia (no desire to eat), Dr. Nelson said. Patients generally fail to report early satiety unless questioned, although it occurs in about 50% of patients and can contribute to anorexia. Early satiety is more common in women.

Satiety results from overlapping stimuli from the CNS and GI tract that affect food intake. One of the common causes is reduced upper GI motility.

Treatment for early satiety includes eating small meals, with the largest meal taken early in the day. Also, patients should avoid drinking liquids at mealtimes because liquids can cause overdistention. Prokinetic agents such as metoclopramide, domperidone (Motilium), and cisapride (Propulsid) may be of value in patients with early satiety, Dr. Nelson said, although the side effects of these agents, including akathisia, insomnia or sedation, colic, and dystonic reaction (jumpy legs), may limit their use.