Symptom management: An important part of cancer care
ABSTRACTPhysicians can do a better job of palliating symptoms and improving the quality of life of cancer patients if they understand the principles of symptom management. We review the general principles of symptom management for fatigue, anorexia, constipation, dyspnea, nausea, and vomiting.
KEY POINTS
- Patients with advanced cancer typically suffer from multiple concurrent symptoms, which they rate as moderate or severe.
- The principles of symptom management include taking an aggressive detailed approach, prioritizing, and identifying symptom pathophysiology.
- Prescribed regimens should be specific and simple; physicians should consider the patient’s age and fragility, the cost of the treatment, and anticipated drug side effects.
- To ensure optimal palliation with the fewest possible adverse effects, reassess frequently, make one change at a time, and use rescue doses.
CONSTIPATION SHOULD BE ANTICIPATED, AND PREVENTED IF POSSIBLE
Constipation is variably defined by patients and health care professionals, but it usually includes components of the Rome II criteria, ie, two or more of the following symptoms28:
- Straining at least 25% of the time
- Hard stools at least 25% of the time
- Incomplete evacuation at least 25% of the time
- Two or fewer bowel movements per week.
These criteria were intended to describe functional constipation in a healthy population.27
More than 50% of patients with advanced cancer report constipation,1 and in those on opioids, the scope of the problem is larger. In addition to binding central nervous system receptors to mediate pain perception, opioids bind systemic receptors including those in the gut. As a result, opioids interfere with smooth muscle tone and contractility, lengthen transit time, promote dry stools, and increase anal sphincter tone.29 A nursing study found that when patients taking opioids were screened for constipation, 95% identified it as the major adverse effect of their pain regimen.30
Multiple causes of constipation
Factors that can cause or contribute to constipation include:
- Dietary factors such as a generally low intake of food, and specifically of fiber
- Inactivity
- Confusion
- Dehydration
- Intestinal obstruction
- Cormorbidities such as diabetes mellitus, hypothyroidism, hypercalcemia
- Uncomfortable toilet arrangements
- Drugs such as opioids (as noted above), anticholinergics, antihypertensives, antacids, diuretics, and iron supplements.
Take a proactive approach to constipation
Constipation is expected in a number of clinical scenarios, such as with the use of opioids or with limited mobility. Patients often attribute constipation to diminished oral intake. But despite low oral intake, regular, smaller-caliber bowel movements are important to ensure that sloughed bowel endothelium and bacteria are eliminated.
Although little evidence supports the use of one standard bowel regimen, prevention is essential. The goal is a soft bowel movement every 1 to 2 days. Constipation prophylaxis should be started at the initiation of any regular opioid regimen. Encouraging physical activity and oral fluid intake and creating a favorable environment for elimination may also help manage constipation.
In our practice, we use a softening agent such as docusate sodium (Colace) 100 mg twice daily, and add a laxative agent such as senna (Senokot) or a magnesium-based osmotic agent as needed. Bulking agents such as over-the-counter fiber supplements should be used with caution in opioid-related constipation. If there has been no bowel movement for 48 hours, a rectal suppository or enema is used. Suppositories or enemas can be scheduled regularly for bedbound patients with chronic constipation.
Methylnaltrexone (Relistor), a mu-opioid antagonist, is a new agent that blocks peripheral opioid receptors in the gut. In a randomized study of 133 patients, methylnaltrexone produced laxation within 4 hours of administration in 48%.31 This methylated, charged compound does not significantly cross the blood-brain barrier and therefore does not interfere with analgesia or cause opioid withdrawal. The dose is 8 mg or 12 mg subcutaneously (based on weight), which can be repeated in 48 hours. If laxation does not occur after one to three doses, other causes of constipation should be explored.
Methylnaltrexone is contraindicated in patients with bowel obstruction, even if the obstruction is thought to be secondary to opioids. Adverse effects include abdominal pain, flatulence, and nausea.
NAUSEA AND VOMITING: NOT ALWAYS DUE TO CHEMOTHERAPY
Nausea (the sensation of the need to vomit) and vomiting (the forceful expulsion of gastric contents) are common symptoms in advanced cancer and are not necessarily related to chemotherapy or radiation therapy. About 60% of cancer patients have nausea, and about 30% vomit.32 Both symptoms are very distressing and diminish quality of life.
Look for potentially reversible causes of nausea and vomiting
Identifying the cause, which is sometimes reversible, may help direct treatment. Potentially reversible causes include:
- Drugs
- Uremia
- Infection
- Anxiety
- Constipation
- Gastric irritation
- Proximal gastrointestinal obstruction.
In a prospective study of 121 patients with advanced cancer, the most common causes of nausea and vomiting were impaired gastric emptying, chemical and metabolic factors (drugs, organ failure, electrolyte disturbance, infection), and bowel obstruction.33–35
Management of nausea and vomiting
Management of nausea and vomiting may require multiple antiemetics, which may need to be given intravenously or subcutaneously.33
The choice of drugs depends on the cause of the nausea
The evidence-based choice of drugs for nausea depends on the cause33–35:
- Nausea due to chemical or metabolic factors: haloperidol (Haldol), levomepromazine (another antipsychotic drug, not available in the United States), cyclizine (Marezine)
- Nausea due to gastric stasis, outlet obstruction: metoclopramide, domperidone (a similar drug, not available in the United States), levomepromazine
- Nausea due to regurgitation: metoclopramide, cyclizine, haloperidol, levomepromazine
- Nausea due to bowel obstruction: metoclopramide (if obstruction is not complete), domperidone, cyclizine, levomepromazine, octreotide (Sandostatin), hyoscyamine (Levsin)
- Nausea due to cranial disease: cyclizine, levomepromazine
- Movement-related nausea: cyclizine, levomepromazine, hyoscyamine
- Cause unclear or multiple causes: cyclizine, haloperidol, levomepromazine
- Cortical nausea: lorazepam (Ativan).
Metoclopramide. If complete bowel obstruction is not suspected, oral metoclopramide, a dopamine antagonist, is our choice for first-line drug therapy.32 Adverse effects include abdominal pain, diarrhea, and sedation.
Haloperidol, another dopamine antagonist, can also be used.32 Haloperidol may cause sedation and is associated with a prolonged QTc interval. Care should be taken in those at risk for dysrhythmia or arrhythmia.
Olanzapine (Zyprexa) is an alternative antipsychotic for patients who cannot tolerate or do not respond to metoclopramide and haloperidol.
Ondansetron (Zofran), a serotonin 5-HT3 receptor antagonist, is usually reserved for nausea and vomiting associated with chemotherapy or radiation, but it can be used in advanced cancer if the above agents fail.37
