Gastrointestinal Complications (PDQ®): Supportive care - Health Professional Information [NCI]

Overview

Gastrointestinal complications such as constipation, fecal impaction, bowel obstruction, diarrhea, and radiation enteritis are common problems for patients with cancer. The growth and spread of cancer, as well as its treatment, contribute to these conditions.

This summary reviews the definitions, causes, assessment, and treatment of each of these common gastrointestinal side effects. For information about treatment-related nausea and vomiting, see Nausea and Vomiting Related to Cancer Treatment.

Constipation is the slow movement of feces through the large intestine that results in the passage of dry, hard stool. This condition can result in discomfort or pain.[1] The longer the transit time of stool in the large intestine, the greater the fluid absorption and the drier and harder the stool becomes.

Constipation may be annoying and uncomfortable, but fecal impaction can be life-threatening. Impaction is the accumulation of dry, hardened feces in the rectum or colon. The patient with a fecal impaction may present with circulatory, cardiac, or respiratory symptoms rather than with gastrointestinal symptoms.[2] If the fecal impaction is not recognized, the signs and symptoms may progress and result in death.

In contrast to constipation and impaction, a bowel obstruction is a partial or complete occlusion of the bowel lumen by a process other than fecal impaction. Intestinal obstructions can be classified by the type of obstruction, the obstructing mechanism, and the part of the bowel involved.

Diarrhea can occur throughout cancer care, and the effects can be physically and emotionally devastating. Although less prevalent than constipation, diarrhea remains a significant symptom burden for people with cancer. Specific definitions of diarrhea vary widely. Acute diarrhea is generally considered to be an abnormal increase in stool liquid and the passage of more than three unformed stools during a 24-hour period.[3] Diarrhea is considered chronic when it persists longer than 4 weeks. This condition can have a significant impact on quality of life and, if severe, may even be life-threatening. Furthermore, diarrhea can lead to increased caregiver burden.

Radiation enteritis is a functional disorder of the large and small bowel that occurs during or after a course of radiation therapy to the abdomen, pelvis, or rectum. One report also documented radiation-induced diarrhea in individuals with lung or head and neck cancers who were receiving radiation with or without chemotherapy.[4]

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

References:

1. Larkin PJ, Cherny NI, La Carpia D, et al.: Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol 29 (Suppl 4): iv111-iv125, 2018.
2. Hussain ZH, Whitehead DA, Lacy BE: Fecal impaction. Curr Gastroenterol Rep 16 (9): 404, 2014.
3. Moschen AR, Sammy Y, Marjenberg Z, et al.: The Underestimated and Overlooked Burden of Diarrhea and Constipation in Cancer Patients. Curr Oncol Rep 24 (7): 861-874, 2022.
4. Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015.

Constipation

Causes of Constipation

Constipation can be a presenting symptom of cancer, or it can occur later as a side effect of a growing tumor or treatment of the tumor. For patients with cancer, other causative factors include the following:[1,2]

• Medications (e.g., chemotherapy drugs, opioids, antacids, diuretics).
• Diet (inadequate fluid intake, inadequate intake of dietary fiber, decreased appetite).
• Prolonged immobility and/or inadequate exercise.
• Bowel disorders (e.g., inflammatory bowel disease, diverticulitis).
• Neuromuscular disorders (disruption of innervation leading to atony of the bowel, spinal cord injury or compression).
• Metabolic disorders (e.g., dehydration, hypercalcemia, hypokalemia, uremia).
• Depression.
• Environmental factors (lack of privacy, change in bathroom habits, assistance to get to the bathroom).

Any of these factors can occur because of the disease process, aging, debilitation, or treatment.

Constipation is frequently the result of autonomic neuropathy caused by vinca alkaloids, oxaliplatin, taxanes, and thalidomide. Other drugs, such as opioid analgesics and anticholinergics (including antidepressants and antihistamines), may lead to constipation by causing decreased sensitivity to the defecation reflex and decreased gut motility. Because constipation is common with the use of opioids, a bowel regimen should be initiated when opioids are prescribed and continued for as long as the patient takes them. Opioids produce varying degrees of constipation, suggesting a dose-related phenomenon. One study suggested that clinicians should not prescribe laxatives based on the opioid dose, but rather should titrate the laxative according to bowel function. Lower doses of opioids or weaker opioids, such as codeine, are just as likely to cause constipation as higher doses and stronger opioids.[3] For more information about opioid-induced constipation, see the Constipation section in Cancer Pain.

Assessment of Constipation

A normal bowel pattern is having at least three stools per week and no more than three stools per day; however, these criteria may be inappropriate for patients with cancer.[4,5]

The following questions may provide a useful assessment guide:

1. What is normal for the patient (frequency, amount, and timing)?
2. When was the last bowel movement? What was the amount, consistency, and color? Was blood passed with it?
3. Has the patient been having any abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas, or rectal fullness?
4. Does the patient regularly use laxatives or enemas? What does the patient usually do to relieve constipation? Does it usually work?
5. What type of diet does the patient follow? How much and what type of fluids are taken on a regular basis?
6. What medications (dose and frequency) is the patient taking?
7. Is this symptom a recent change?
8. How many times a day is flatus passed?

A thorough history of the patient's bowel pattern, dietary changes, and medications, along with a physical examination, can identify possible causes of constipation. The evaluation also includes assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. The following tests may be part of the clinical evaluation:[6]

• Digital rectal exam: Done to rule out fecal impaction at the level of the rectum.
• Fecal occult blood test: Helpful in determining a possible intraluminal lesion.
• Colonoscopy or sigmoidoscopy: Necessary if cancer is suspected.

Physical assessment will determine the presence or absence of bowel sounds, flatus, or abdominal distention. Patients with colostomies are assessed for constipation. Dietary habits, fluid intake, activity levels, and use of opioids in these patients are examined.

Management of Constipation

Comprehensive management of constipation includes prevention (if possible), elimination of causative factors, and judicious use of laxatives. Some patients can be encouraged to increase dietary fiber (fruits; green, leafy vegetables; 100% whole-grain cereals and breads; and bran) and to drink eight 8-oz. (240-mL) glasses of fluid daily unless contraindicated. For more information, see Nutrition in Cancer Care.

Nonpharmacological interventions

The following interventions may be done before or with the use of pharmacological agents:

• Record bowel movements daily.
• Encourage patient to increase fluid intake, unless contraindicated.
• Encourage regular exercise, including abdominal exercises in bed or moving from bed to chair if the patient is not ambulatory.
• Encourage adequate fiber intake.
• Provide a warm or hot drink approximately one-half hour before time of patient's usual defecation.
• Provide privacy and quiet time at the patient's usual or planned time for defecation.
• Provide a toilet or bedside commode and appropriate assistive devices; avoid bedpan use whenever possible.

Contraindications

Rectal agents should be avoided in patients with cancer at risk of thrombocytopenia, leukopenia, and/or mucositis from cancer and its treatment. In immunocompromised patients, manipulation of the rectum and anus should be avoided (i.e., no rectal examinations, no suppositories, and no enemas). These actions can lead to the development of anal fissures or abscesses, which are portals of entry for infection. Also, the stoma of a patient with neutropenia should not be manipulated unnecessarily.

Transanal irrigation is a procedure in which water is introduced into the bowel through the anus. A systematic review suggested that this procedure may be beneficial for patients with neurogenic bowel disease, low anterior resection syndrome, fecal incontinence, and chronic constipation. However, its efficacy is unknown in patients with cancer who have constipation.[7]

Medical agents for constipation

There are different medical agents used to treat constipation. Table 1 lists these agents in more detail.

Table 1. Medical Agents for Constipation

Name	Action	Caution/Side Effects	Onset	Selected Drugs/Dosages
GI = gastrointestinal; IBS = irritable bowel syndrome; N/A = not applicable; PO = orally.
Bulk producers	Natural or semisynthetic polysaccharide and cellulose that work with the body's natural processes to hold water in intestinal tract, soften stool, and increase frequency of stool passage.	To reduce risk of bowel obstruction, take with two 8-oz. (240-mL) glasses of water and maintain adequate hydration.	12–24 h (may be delayed up to 72 h)	Methylcellulose: 2 g dissolved in 8-oz. (240-mL) glass of water PO up to three times daily. Increase as needed by 2 g.
		Avoid if fecal impaction or intestinal obstruction is suspected.
		Not advised for opioid-induced constipation.		Psyllium: 2.5-30 g PO daily in divided doses.
Saline laxatives	High osmolarity attracts water into lumen of the intestines. Fluid accumulation alters stool consistency, distends bowel, and induces peristaltic movement.	Repeated use can alter fluid and electrolyte balance.	0.5–6 h	Magnesium sulfate: 10–20 g dissolved in 8-oz. (240-mL) glass of water orally. May repeat in 4 h. Do not exceed two doses daily.
				Magnesium hydroxide:
					– 400 mg/5 mL liquid: 30–60 mL/day once daily at bedtime or divided.
					– 800 mg/5 mL liquid: 15–30 mL/day once daily at bedtime or divided.
					– 1,200 mg/5 mL liquid: 10–20 mL/day once daily at bedtime or divided.
		Avoid magnesium-containing laxatives in patients with renal dysfunction. Avoid sodium-containing laxatives in patients with edema, congestive heart failure, megacolon, or hypertension.		Magnesium citrate: 195–300 mL as single dose or divided doses over 24 h.
	Used to clear bowels for rectal or bowel examination.	Sodium phosphate enemas can cause acute phosphate nephropathy. Cramps may occur.		Sodium phosphate: 4.5-oz. enema as single dose.
Stimulant laxatives	Increase motor activity of bowels by direct action on smooth muscle of the intestine.	Prolonged use causes laxative dependency and loss of normal bowel function.	6–24 h (oral), 0.25-1 h (bisacodyl suppository)	Sennosides: 17.2–34.4 mg PO once or twice daily.
		Bisacodyl must be excreted in bile to be active and is not effective with biliary obstruction or diversion. Avoid bisacodyl with known or suspected ulcerative lesions of the colon. May cause cramping.
	Used to clear bowels for rectal or bowel examination.	Avoid taking bisacodyl within 1 h of taking antacids, milk, or cimetidine; causes premature dissolving of enteric coating, which results in gastric or duodenal stimulation.		Bisacodyl: 5–15 mg PO once daily or 10-mg suppository once daily.
Lubricant laxatives	Lubricate intestinal mucosa and soften stool to help prevent straining in patients for whom straining would be dangerous.	Give on empty stomach at bedtime. Mineral oil prevents absorption of oil-soluble vitamins and drugs.	6–8 h (oral), 2-15 min (rectal)	Mineral oil (oral):
		With older patients, avoid mineral oil due to aspiration potential that can cause lipid pneumonitis.
		Can interfere with postoperative healing of anorectal surgery.			– Nonemulsified: 15–45 mL in 24 h.
					– Emulsified: 30–90 mL daily as single dose or divided.
		Avoid giving with docusate sodium, which causes increased systemic absorption of mineral oil.		Mineral oil (rectal): 118 mL as single dose.
Fecal softeners	Promote water retention, softening stool to prevent straining; most beneficial when stool is hard. Stool softeners and emollient laxatives are of limited use because of colonic resorption of water from the forming stool.	May increase systemic absorption of mineral oil when administered together.	Up to 3 d	Docusate sodium: 50–240 mg taken with full glass of water.
				Docusate calcium: 240 mg daily until bowel movement is normal.
	Not used as sole regimen but may be useful in combination with stimulant laxatives.			Docusate potassium: 100–300 mg daily until bowel movement is normal; increase daily fluid intake.
Lactulose	Synthetic disaccharide that passes to colon undigested. When broken down in colon, it produces lactic acid, formic acid, acetic acid, and carbon dioxide. These products increase osmotic pressure, increasing amount of water held in stool, which softens stool and increases frequency of passage.	Excessive amounts may cause diarrhea with electrolyte losses.	24–48 h	10–20 g PO daily; may increase to 40 g daily.
		Avoid in patients with acute abdomen, fecal impaction, or bowel obstruction.
Polyethylene glycol and electrolytes	Used to clear bowel with minimal water and sodium loss or gain.	Contraindicated in patients with bowel obstruction.	24–96 h	17 g dissolved in 4-8 oz. (120–240 mL) of beverage once daily.
Opioid antagonists	Restricted ability to cross blood-brain barrier.	Give only if other drugs have failed. Contraindicated in patients with bowel obstruction.	In a study of patients with advanced, cancer and other diseases, about 50% of patients defecated within 4 h of receiving the injection.[8,9]	Naloxone: Oral oxycodone: naloxone combination in ratio of 2:1[10]
				Methylnaltrexone: Subcutaneous 0.15 mg/kg daily or every other day to treat opioid-induced constipation.
				Naldemedine: 0.2 mg PO daily for 2 wk[11]
	Block opioid receptors peripherally in the GI tract to reverse opioid-induced decreases in intestinal motility.	Side effects: Dizziness, nausea, abdominal pain, flatulence, diarrhea.	No evidence of withdrawal or other central effects of the opioid; pain scores remained unchanged.	Naloxegol: 12.5–25 mg PO daily
Lubiprostone	Chloride channel activator that acts to increase intestinal fluid secretion and improve fecal transit, bypassing antisecretory effects of opiates.	Contraindicated in patients with bowel obstruction.	24–48 h in chronic constipation.[12]	24 µg PO twice daily (8 µg PO twice daily in IBS).
		Dyspnea and chest tightness may occur within 30-60 min of first dose and resolve within a few hours. Syncope and hypotension, some requiring hospitalization, may also occur.
	Used for chronic idiopathic constipation, IBS with constipation, and opioid-induced constipation.	Side effects: Diarrhea, nausea, headache, abdominal pain.
Linaclotide	Guanylate cyclase-C agonist that causes increased chloride and bicarbonate secretion into the intestinal lumen, leading to increased intestinal fluid and GI transit.	Contraindicated in patients <2 y and in patients with mechanical GI obstruction.	N/A	145 µg PO daily (72 µg PO daily for tolerability or 290 µg PO daily in IBS).
		May cause severe diarrhea associated with syncope, hypertension, and electrolyte abnormalities.
	Used for chronic idiopathic constipation, IBS with constipation.	Side effects: Diarrhea, headache, abdominal pain.
Prucalopride	Selective 5-HT4 receptor agonist that stimulates peristaltic reflux and increases intestinal secretions and GI motility.	Contraindicated in patients with intestinal perforation or obstruction due to structural or functional disorder of the gut wall, obstructive ileus, or severe inflammatory conditions of the GI tract.	N/A	2 mg PO daily
	Used for chronic idiopathic constipation.	Side effects: Diarrhea, nausea, headache, abdominal pain.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Lindberg G, Hamid SS, Malfertheiner P, et al.: World Gastroenterology Organisation global guideline: Constipation--a global perspective. J Clin Gastroenterol 45 (6): 483-7, 2011.
2. Davies A, Leach C, Caponero R, et al.: MASCC recommendations on the management of constipation in patients with advanced cancer. Support Care Cancer 28 (1): 23-33, 2020.
3. Bennett M, Cresswell H: Factors influencing constipation in advanced cancer patients: a prospective study of opioid dose, dantron dose and physical functioning. Palliat Med 17 (5): 418-22, 2003.
4. Portenoy RK: Constipation in the cancer patient: causes and management. Med Clin North Am 71 (2): 303-11, 1987.
5. McShane RE, McLane AM: Constipation. Consensual and empirical validation. Nurs Clin North Am 20 (4): 801-8, 1985.
6. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994.
7. Mekhael M, Kristensen HØ, Larsen HM, et al.: Transanal Irrigation for Neurogenic Bowel Disease, Low Anterior Resection Syndrome, Faecal Incontinence and Chronic Constipation: A Systematic Review. J Clin Med 10 (4): , 2021.
8. Thomas J, Karver S, Cooney GA, et al.: Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 358 (22): 2332-43, 2008.
9. Portenoy RK, Thomas J, Moehl Boatwright ML, et al.: Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 35 (5): 458-68, 2008.
10. Meissner W, Leyendecker P, Mueller-Lissner S, et al.: A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain 13 (1): 56-64, 2009.
11. Katakami N, Harada T, Murata T, et al.: Randomized Phase III and Extension Studies of Naldemedine in Patients With Opioid-Induced Constipation and Cancer. J Clin Oncol 35 (34): 3859-3866, 2017.
12. Thayalasekeran S, Ali H, Tsai HH: Novel therapies for constipation. World J Gastroenterol 19 (45): 8247-51, 2013.

Fecal Impaction

Causes of Fecal Impaction

Constipation, if left untreated, may lead to fecal impaction. The causes of impaction are the same as the causes of constipation.[1] For more information, see the Causes of Constipation section.

Signs and Symptoms of Fecal Impaction

The patient may exhibit symptoms similar to those of constipation or present with symptoms unrelated to the gastrointestinal system. If the fecal impaction presses on the sacral nerves, the patient may experience back pain. If the impaction presses on the ureters, bladder, or urethra, urinary symptoms, such as urinary retention or increased or decreased frequency or urgency of urination, may develop.

When abdominal distention occurs, movement of the diaphragm may be compromised, which can lead to insufficient aeration with subsequent hypoxia and/or left ventricular dysfunction. Hypoxia can, in turn, precipitate angina or tachycardia. If the vasovagal response is stimulated by the pressure of impaction, the patient may become dizzy and hypotensive.

Movement of stool around the impaction may result in diarrhea, which can be explosive. Coughing or activities that increase intra-abdominal pressure may cause leakage of stool. The leakage may be accompanied by nausea, vomiting, abdominal pain, and dehydration and is virtually diagnostic of the condition. The patient with an impaction may present in an acutely confused and disoriented state, with signs of tachycardia, diaphoresis, fever, elevated or low blood pressure, and/or abdominal fullness or rigidity.

Assessment of Fecal Impaction

Assessment of fecal impaction includes the same questions as for the patient with constipation. Additional assessment includes auscultation of bowel sounds to determine if they are present, absent, hyperactive, or hypoactive. The abdomen is inspected for distention and gently palpated for any masses, rigidity, or tenderness. A rectal examination will determine the presence of stool in the rectum or sigmoid colon. An abdominal x-ray (flat and upright) will show loss of haustral markings, gas patterns reflecting gross amounts of stool, and dilatation proximal to the impaction.[2] For more information, see the Assessment of Constipation section.

Treatment of Fecal Impaction

The primary treatment of impaction is to hydrate and soften the stool so that it can be removed or passed. Enemas (oil retention, tap water, or hypertonic phosphate) lubricate the bowel and soften the stool. Caution must be exercised in that fecal impaction can irritate the bowel wall, and excess enemas may perforate the bowel. The patient may need to be digitally disimpacted if the stool is within reach. This is best done after administering an enema to lubricate the bowel.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Davies A, Leach C, Caponero R, et al.: MASCC recommendations on the management of constipation in patients with advanced cancer. Support Care Cancer 28 (1): 23-33, 2020.
2. Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994.

Large or Small Bowel Obstruction

There are four types of bowel obstruction that include the following:

1. Simple. An obstruction is blocked in one place.
2. Closed-loop. An obstruction is blocked in two places. This type may develop when the bowel twists around on itself, isolating the looped section of the bowel and obstructing the portion above it.
3. Strangulated. There is decreased blood flow to the bowel that, if not relieved, will develop into an incarcerated obstruction.
4. Incarcerated. The bowel becomes necrotic.

Causes of Bowel Obstruction

The obstructing mechanism can be extrinsic or intrinsic.[1]

Extrinsic causes include the following:

• Inflammation or trauma to the bowel.
• Neoplasms.
• Adhesions.
• Hernias.
• Volvulus.
• Compression from outside the intestinal tract.

Intrinsic causes include the following:

• Paralytic ileus.
• Mesenteric embolus or thrombus.
• Tumor infiltration of the mesentery, bowel muscle, or celiac and enteric plexuses.[2]
• Endometriosis.

Bowel obstructions are more common in the small intestine than in the colon.[3] Bowel obstructions are frequently seen in the ileum. Small bowel obstructions are often caused by adhesions or hernias, while large bowel obstructions are usually caused by carcinomas, volvulus, or diverticulitis. The presentation of obstruction will relate to whether the small or large intestine is involved.

The most common malignancies that cause bowel obstruction are cancers of the colon, stomach, and ovary.[3] Patients who have had abdominal surgery or abdominal radiation are also at higher risk of developing bowel obstruction. Bowel obstructions are most common during advanced stages of disease.

Assessment and Diagnosis of Bowel Obstruction

Possible symptoms of malignant bowel obstruction include abdominal pain, cramps, distention, nausea, vomiting, absence of gas and stool passage, and, rarely, overflow diarrhea.[3] A complete blood cell count, electrolyte panel, and urinalysis are obtained to evaluate fluid and electrolyte imbalance and/or sepsis. An elevated white blood cell count (15,000–20,000/mm³) suggests bowel necrosis.

Traditionally, flat and upright abdominal films have been used for diagnosis. However, x-rays have only modest sensitivity to detect a bowel obstruction and limited ability to detect the exact site, cause, or complications. Contrast computed tomography (CT) delivers enhanced diagnostic precision. A CT of the abdomen and pelvis with intravenous contrast and/or a CT enterography may be used to diagnose patients suspected of having a small bowel obstruction.[4,5]

Treatment of Acute Bowel Obstruction

Careful serial examinations are necessary to manage patients with progressive abdominal symptoms that may be due to acute bowel obstruction. The principles of supportive care in this setting include bowel rest, volume resuscitation, correction of electrolyte imbalances, and transfusion support if necessary. These measures may precede or accompany decompression efforts.

When bowel obstruction is partial, decompression of the distended bowel may be attempted with nasogastric tubes (NGTs) or intestinal tubes. The use of these tubes may reduce edema, relieve fluid and gas accumulation, or decrease the need for multiple stage procedures.[6] However, surgery may be necessary within 24 hours if there is complete, acute obstruction. The use of self-expandable stents to decompress complete, acute malignant bowel obstruction has been noted to decrease the frequency of unnecessary surgery. The stents permit staging of the disease, increase the rate of primary anastomosis relative to colostomy, and decrease morbidity in patients with left-sided colon and rectal malignancies. Further study is warranted, including cost analysis.[7]

Management of Chronic, Malignant Bowel Obstruction

Patients with advanced cancer may have chronic, progressive bowel obstruction that is inoperable.[8,9] The most frequent causes of inoperability are extensive tumor and multiple partial obstructions.[10,11][Level of evidence: II][12] A retrospective review evaluated surgical palliation of malignant bowel obstruction secondary to peritoneal carcinomatosis in 63 patients with nongynecological cancers. The ability to tolerate solid food at hospital discharge was the criterion for successful palliation. Multiple logistic regression analysis identified the absence of ascites and obstruction not involving the small bowel as predictors of successful surgical palliation in this population. Successful palliation was achieved in 45% of patients and was maintained in 76% of this group at a median follow-up of 78 days, for an overall success rate of 35%. The postoperative mortality rate was 15%, and postoperative complications occurred in 44% of patients.[13]

For some patients with malignant obstructions of the gastrointestinal tract, the use of expandable metal stents may provide palliation of obstructive symptoms. Esophageal, biliary, gastroduodenal, and colorectal stents are available.[7,14,15,16,17,18,19] They may be placed under endoscopic guidance, with or without fluoroscopy, or by an interventional radiologist using fluoroscopy. Morbidity with stent placement may be lower than with surgery. Adequate imaging of the stricture itself and the gastrointestinal tract distal to the stricture is recommended to assess stricture length, detect multifocal disease, and determine the appropriateness of stenting.[20,21][Level of evidence: II][22]

When neither surgery nor stenting is possible, the accumulation of the unabsorbed secretions produce nausea, vomiting, pain, and colicky activity as a result of the partial or complete occlusion of the lumen. In this case, temporary decompression may be accomplished using an NGT; however, NGTs are not favored as a long-term solution.[3] Instead, a gastrostomy tube is commonly used to provide decompression of air and fluid that may accumulate and cause visceral distention and pain. The gastrostomy tube is placed into the stomach and is attached to a drainage bag that can be easily concealed under clothing. When the valve between the gastrostomy tube and the bag is open, the patient may be able to eat or drink by mouth without creating discomfort since the food is drained directly into the bag. Dietary discretion is advised to minimize the risk of tube obstruction by solid food. If the obstruction improves, the valve can be closed, and the patient may once again benefit from enteral nutrition.

Sometimes, decompression is difficult even with a gastrostomy tube in place. Accumulation of fluid may interfere with decompression because several liters of gastrointestinal secretions may be produced per day. Pharmacological symptom management may be necessary. In the case of complete obstruction, avoid oral administration of medications if possible. To relieve continuous abdominal pain, opioid analgesics may be necessary. Associated nausea and vomiting may be treated with several different medications, including scopolamine, octreotide, dexamethasone, haloperidol, metoclopramide, dimenhydrinate, prochlorperazine, serotonin antagonists, and olanzapine.[3] Effective antispasmodics in this situation include anticholinergics (such as scopolamine) [23] and possibly corticosteroids, as well as centrally acting agents.

Careful use of laxatives may be considered for constipation associated with partial bowel obstruction. However, a 2022 systematic review did not identify any studies that examined laxatives in this setting.[3] Osmotic laxatives, such as polyethylene glycol 3350, pull water into the lumen of the bowel, softening stool and increasing peristalsis. Bulk-forming laxatives such as psyllium should be avoided because they increase stool volume and can worsen the obstruction. Finally, manual disimpaction may be necessary if fecal impaction is noted during physical examination.

Another option for management of refractory pain and/or nausea is the synthetic somatostatin analogue octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions.[24,25][Level of evidence: I][26]

Octreotide is usually given subcutaneously at 50 to 200 µg three times per day and may reduce the nausea, vomiting, and abdominal pain of malignant bowel obstruction. For select patients in whom octreotide alone is ineffective, the addition of an anticholinergic such as scopolamine may help reduce the associated painful colic of malignant bowel obstruction. When either scopolamine or octreotide is used alone, each is ineffective.[14,27,28,29] Corticosteroids are widely used to treat bowel obstruction, but empirical support is limited.[30]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Rami Reddy SR, Cappell MS: A Systematic Review of the Clinical Presentation, Diagnosis, and Treatment of Small Bowel Obstruction. Curr Gastroenterol Rep 19 (6): 28, 2017.
2. Cousins SE, Tempest E, Feuer DJ: Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer. Cochrane Database Syst Rev (1): CD002764, 2016.
3. Madariaga A, Lau J, Ghoshal A, et al.: MASCC multidisciplinary evidence-based recommendations for the management of malignant bowel obstruction in advanced cancer. Support Care Cancer 30 (6): 4711-4728, 2022.
4. Lee YC, Jivraj N, O'Brien C, et al.: Malignant Bowel Obstruction in Advanced Gynecologic Cancers: An Updated Review from a Multidisciplinary Perspective. Obstet Gynecol Int 2018: 1867238, 2018.
5. Chang KJ, Marin D, Kim DH, et al.: ACR Appropriateness Criteria® Suspected Small-Bowel Obstruction. J Am Coll Radiol 17 (5S): S305-S314, 2020.
6. Horiuchi A, Maeyama H, Ochi Y, et al.: Usefulness of Dennis Colorectal Tube in endoscopic decompression of acute, malignant colonic obstruction. Gastrointest Endosc 54 (2): 229-32, 2001.
7. Martinez-Santos C, Lobato RF, Fradejas JM, et al.: Self-expandable stent before elective surgery vs. emergency surgery for the treatment of malignant colorectal obstructions: comparison of primary anastomosis and morbidity rates. Dis Colon Rectum 45 (3): 401-6, 2002.
8. Ripamonti C, Bruera E: Palliative management of malignant bowel obstruction. Int J Gynecol Cancer 12 (2): 135-43, 2002 Mar-Apr.
9. Potluri V, Zhukovsky DS: Recent advances in malignant bowel obstruction: an interface of old and new. Curr Pain Headache Rep 7 (4): 270-8, 2003.
10. Jung GS, Song HY, Kang SG, et al.: Malignant gastroduodenal obstructions: treatment by means of a covered expandable metallic stent-initial experience. Radiology 216 (3): 758-63, 2000.
11. Camúñez F, Echenagusia A, Simó G, et al.: Malignant colorectal obstruction treated by means of self-expanding metallic stents: effectiveness before surgery and in palliation. Radiology 216 (2): 492-7, 2000.
12. Coco C, Cogliandolo S, Riccioni ME, et al.: Use of a self-expanding stent in the palliation of rectal cancer recurrences. A report of three cases. Surg Endosc 14 (8): 708-11, 2000.
13. Blair SL, Chu DZ, Schwarz RE: Outcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol 8 (8): 632-7, 2001.
14. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.
15. Law WL, Chu KW, Ho JW, et al.: Self-expanding metallic stent in the treatment of colonic obstruction caused by advanced malignancies. Dis Colon Rectum 43 (11): 1522-7, 2000.
16. Repici A, Reggio D, De Angelis C, et al.: Covered metal stents for management of inoperable malignant colorectal strictures. Gastrointest Endosc 52 (6): 735-40, 2000.
17. Harris GJ, Senagore AJ, Lavery IC, et al.: The management of neoplastic colorectal obstruction with colonic endolumenal stenting devices. Am J Surg 181 (6): 499-506, 2001.
18. Aviv RI, Shyamalan G, Watkinson A, et al.: Radiological palliation of malignant colonic obstruction. Clin Radiol 57 (5): 347-51, 2002.
19. Dauphine CE, Tan P, Beart RW, et al.: Placement of self-expanding metal stents for acute malignant large-bowel obstruction: a collective review. Ann Surg Oncol 9 (6): 574-9, 2002.
20. Lopera JE, Alvarez O, Castaño R, et al.: Initial experience with Song's covered duodenal stent in the treatment of malignant gastroduodenal obstruction. J Vasc Interv Radiol 12 (11): 1297-303, 2001.
21. Razzaq R, Laasch HU, England R, et al.: Expandable metal stents for the palliation of malignant gastroduodenal obstruction. Cardiovasc Intervent Radiol 24 (5): 313-8, 2001 Sep-Oct.
22. Baron TH, Rey JF, Spinelli P: Expandable metal stent placement for malignant colorectal obstruction. Endoscopy 34 (10): 823-30, 2002.
23. De Conno F, Caraceni A, Zecca E, et al.: Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction. J Pain Symptom Manage 6 (8): 484-6, 1991.
24. Ripamonti C, Mercadante S, Groff L, et al.: Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. J Pain Symptom Manage 19 (1): 23-34, 2000.
25. Mystakidou K, Tsilika E, Kalaidopoulou O, et al.: Comparison of octreotide administration vs conservative treatment in the management of inoperable bowel obstruction in patients with far advanced cancer: a randomized, double- blind, controlled clinical trial. Anticancer Res 22 (2B): 1187-92, 2002 Mar-Apr.
26. Fallon MT: The physiology of somatostatin and its synthetic analogue, octreotide. European Journal of Palliative Care 1 (1): 20-2, 1994.
27. Mercadante S: Assessment and management of mechanical bowel obstruction. In: Portenoy RK, Bruera E, eds.: Topics in Palliative Care. Volume 1. Oxford University Press, 1997, pp. 113-30.
28. Fainsinger RL: Integrating medical and surgical treatments in gastrointestinal, genitourinary, and biliary obstruction in patients with cancer. Hematol Oncol Clin North Am 10 (1): 173-88, 1996.
29. Ripamonti C, Panzeri C, Groff L, et al.: The role of somatostatin and octreotide in bowel obstruction: pre-clinical and clinical results. Tumori 87 (1): 1-9, 2001 Jan-Feb.
30. Davis M, Hui D, Davies A, et al.: Medical management of malignant bowel obstruction in patients with advanced cancer: 2021 MASCC guideline update. Support Care Cancer 29 (12): 8089-8096, 2021.

Diarrhea

The prevalence and severity of diarrhea in patients with cancer vary greatly. Some chemotherapeutic regimens, particularly those containing fluoropyrimidines or irinotecan, are associated with diarrhea rates as high as 50% to 80%.[1] Gastrointestinal toxicity, ranging from diarrhea to severe colitis, is an immune-related adverse effect associated with immune checkpoint inhibitor (ICI) treatment. The rate of diarrhea appears to be dose dependent with anti-CTLA-4 inhibitors and greater with dual checkpoint inhibitor regimens compared with a single agent.[2,3] Rates of any grade diarrhea are 16% to 37% for single-agent PD-L and PD-L1, 32% to 49% for single-agent anti-CTLA-4, and 17% to 44% for dual ICI regimens.[4,5,6] Diarrhea is also commonly observed in patients with carcinoid tumors who are receiving radiation therapy to abdominal/pelvic fields or undergoing bone marrow transplantation or surgical intervention of the gastrointestinal tract.[7] In a large heterogeneous sample of patients with cancer in various stages of treatment, the prevalence of moderate-to-severe diarrhea was 14%.[8] Among children with cancer during the last month of life, 19% experienced diarrhea.[9]

The consequences of diarrhea can be significant and life-threatening. According to the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events, more than half of patients who received chemotherapy for colorectal cancer experienced diarrhea of grade 3 or 4, requiring treatment changes or the reduction, delay, or discontinuation of therapy (see Table 2).[10,11] A review of several clinical trials of irinotecan plus high-dose fluorouracil and leucovorin for colorectal cancer treatment revealed early death rates of 2.2% to 4.8%, primarily due to gastrointestinal toxicity.[12] With the advent of more aggressive anticancer therapies, the potential physical and psychosocial consequences of diarrhea and its indirect effect on cancer treatment outcomes are likely to expand.[13]

Table 2. National Cancer Institute's Common Terminology Criteria for Adverse Events: Diarrhea^a,b

Grade	Description
ADL = activities of daily living.
a Adapted from National Cancer Institute.[11]
b Definition: A disorder characterized by an increase in frequency and/or loose or watery bowel movements.
c Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
d Self-care ADL refers to bathing, dressing and undressing, feeding oneself, using the toilet, taking medications, and not being bedridden.
1	Increase of <4 stools/day over baseline; mild increase in ostomy output compared with baseline
2	Increase of 4–6 stools/day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADLc
3	Increase of ≥7 stools/day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADLd
4	Life-threatening consequences; urgent intervention indicated
5	Death

Causes of Diarrhea

In patients being treated for cancer, diarrhea is most commonly induced by therapy.[14] Conventional methods of diarrhea-causing treatment include the following:

• Surgery.
• Chemotherapy.
• Immunotherapy.
• Radiation therapy.
• Bone marrow transplantation.

Other causes of acute diarrhea include the following:[15]

• Antibiotic therapy.
• Tube feeding.
• Stress and anxiety associated with cancer diagnosis and treatment.
• Infection.

Typical infections are of viral, bacterial, protozoan, parasitic, or fungal etiology. They may also be caused by pseudomembranous colitis, which often does not respond to treatment.[7]Clostridium difficile is a common cause of pseudomembranous colitis.

Other causes of diarrhea in patients with cancer include the underlying cancer, responses to diet, or concomitant diseases (see Table 3). Common causes of diarrhea in patients receiving palliative care are difficulty adjusting the laxative regimen and impaction leading to leakage of stool around the fecal obstruction.

Surgery, a primary treatment modality for many cancers, can affect the body by mechanical, functional, and physiological alterations. Postsurgical complications of gastrointestinal surgery that affect normal bowel function may contribute to diarrhea.[16]

Certain chemotherapeutic agents can alter normal absorption and secretion functions of the small bowel, resulting in treatment-related diarrhea (see Table 3 and Table 5). Patients who are receiving concomitant abdominal or pelvic radiation therapy or recovering from recent gastrointestinal surgery will often experience more severe diarrhea.

Radiation therapy to abdominal, pelvic, lumbar, or para-aortic fields can result in changes to normal bowel function. Factors contributing to the occurrence and severity of intestinal complications include the following:

• Total dose of radiation.
• Fractionation of radiation.
• Volume of bowel irradiated.
• Concomitant chemotherapy.

Acute intestinal side effects occur at approximately 10 Gy and may last up to 8 to 12 weeks posttherapy. Chronic radiation enteritis may occur months to years after therapy ends. This condition necessitates dietary modification, pharmacological management, and, in some instances, surgical intervention. For more information, see the Radiation Enteritis section.

Graft-versus-host disease (GVHD) is a major complication of allogeneic transplantation. It commonly affects the intestinal tract, skin, and liver. Symptoms of gastrointestinal GVHD include nausea and vomiting, severe abdominal pain and cramping, and watery diarrhea.[17] The volume of accompanying GVHD-associated diarrhea may reach up to several liters per day and is an indicator of the degree and extent of mucosal damage.[17] Acute GVHD is usually manifested within 100 days posttransplant, although it can occur as early as 7 to 10 days posttransplant. It may resolve or develop into a chronic form requiring long-term treatment and dietary management.

Table 3. Possible Contributors to Diarrhea in Patients With Cancer

Cancer[18,19]	Carcinoid syndrome
	Colon cancer
	Lymphoma
	Medullary carcinoma of the thyroid
	Pancreatic cancer, particularly islet cell tumors (Zollinger-Ellison syndrome)
	Pheochromocytoma
Surgery or procedure[20]	Celiac plexus block
	Cholecystectomy, esophagogastrectomy
	Gastrectomy, pancreaticoduodenectomy (Whipple procedure)
	Intestinal resection (malabsorption due to short bowel syndrome)
	Vagotomy
Chemotherapy	See Table 4for more information.
Radiation therapy (For more information, see the Radiation Enteritissection.)[21]	Irradiation to the abdomen, para-aortics, lumbar, and pelvis or radiation for lung and head and neck cancers
Bone marrow transplantation[22]	Conditioning chemotherapy, total-body irradiation, graft-versus-host disease after allogeneic bone marrow or peripheral blood stem cell transplants
Drug adverse effects[18,19]	Antibiotics, magnesium-containing antacids, antihypertensives, colchicine, digoxin, lactulose, laxatives, methyldopa, metoclopramide, misoprostol, potassium supplements, propranolol, theophylline
Concurrent disease[18,19]	Diabetes, hyperthyroidism, inflammatory bowel disease (Crohn disease, diverticulitis, gastroenteritis, HIV/AIDS, ulcerative colitis), obstruction (tumor related)
Infection[23]	Clostridium difficile, Clostridium perfringens, Bacillus cereus, Giardia lamblia, Cryptosporidium, Salmonella, Shigella, Campylobacter, Rotavirus
Fecal impaction[18,19]	Constipation leading to obstruction
Diet[18,19]	Alcohol, milk, dairy products (particularly in patients with lactose intolerance)
	Caffeine-containing products (coffee, tea, chocolate); specific fruit juices (prune juice, unfiltered apple juice, sauerkraut juice)
	High-fiber foods (raw fruits and vegetables, nuts, seeds, whole-grain products, dried legumes); high-fat foods (deep-fried foods, high fat–containing foods)
	Lactulose intolerance or food allergies
	Sorbitol-containing foods (candy and chewing gum); hot and spicy foods; gas-forming foods and beverages (cruciferous vegetables, dried legumes, melons, carbonated beverages)
Psychological factors[19]	Stress

Some chemotherapeutic agents result in grade 3 or 4 treatment-related diarrhea. Table 4 and Table 5 list the toxicity of intravenous and oral agents used to treat cancer, respectively.

Table 4. Rate of Grade 3 or 4 Diarrhea Associated With Intravenous Chemotherapy^a

Chemotherapy Agent	Grade 3 or 4 Diarrhea Rate (%)b	Reference
a Includes drugs with 5% or greater grade 3 or 4 toxicity.
b Highest percentage listed in current manufacturer prescribing information (single-agent rate of diarrhea listed if provided; excludes irinotecan-based combinations).
Irinotecan	31	[24]
Ziv-aflibercept	19	[24]
Irinotecan, liposomal	13	[24]
Fluorouracil	12.7	[25]
Clofarabine	12	[24]
Pertuzumab	12	[24]
Ipilimumab + nivolumab	11	[24]
Bortezomib	7	[24]
Atezolizumab	6	[24]
Azacitidine	6	[24]
Brentuximab vedotin	6	[24]
Cabazitaxel	6	[24]
Docetaxel	6	[24]
Nab-paclitaxel	6	[24]
Cetuximab	5	[24]
Copanlisib	5	[24]
Elotuzumab	5	[24]
Ipilimumab	5	[24]
Nivolumab	5	[24]
Busulfan	5	[26]

·Table 5. Rate of Grade 3 or 4 Diarrhea Associated With Oral Chemotherapy^a

Chemotherapy Agent	Grade 3 or 4 Diarrhea Rate (%)b	Reference
a Includes drugs with 5% or greater grade 3 or 4 toxicity.
b Highest percentage listed in current manufacturer prescribing information (single-agent rate of diarrhea listed if provided; excludes irinotecan-based combinations).
Selumetinib	24	[24]
Tucatinib (with capecitabine/trastuzumab)	13	[27,28]
Vandetanib	10–11	[29,30]
Umbralisib	10	[31]
Vorinostat	5–8	[32,33]
Sunitinib	4–10	[24]
Sotorasib	4	[34,35]
Selinexor	3–7	[36,37,38]
Sorafenib	2–8	[39,40,41]

Assessment of Diarrhea

Rapid yet thorough assessment of diarrhea is imperative because of its potentially life-threatening nature. Few standardized assessment tools are available. As a result, standardized assessment is rare in the clinical setting.[7] For a complete assessment, one author suggests obtaining background information from the patient that includes the type and extent of the patient's cancer, anticancer treatment, comorbid factors, coexisting symptoms, patient and provider perceptions, and a thorough description of the diarrhea. Stringent monitoring conducted at least weekly is indicated during therapy using chemotherapeutic agents known to cause diarrhea.[12] The NCI's Common Terminology Criteria for Adverse Events (see Table 2) evaluate diarrhea by the following:[11]

• Number of stools per day.
• Incontinence.
• Increase in ostomy output compared with baseline.
• Interference with activities of daily living.
• Hospitalization.

The patient history also includes questions regarding the frequency of bowel movements during the past 24 hours, the character of the fecal material, and the time course of the development of diarrhea.[42] A visual tool to assist patients and families in characterizing the consistency of the stool has been developed.[43] Six diagrams illustrate fecal material consistency ranging from well-formed, formed, and semiformed to loose, very loose, and liquid.

Patients are questioned regarding related symptoms that might indicate hemodynamic compromise or the underlying etiology. Specific questions include information about the following:

• Dizziness.
• Orthostatic symptoms.
• Lethargy.
• Cramping.
• Abdominal pain.
• Nausea.
• Vomiting.
• Fever.
• Rectal bleeding.

These symptoms are classified as complicated or uncomplicated, with therapy based on these classifications.[44]

Uncomplicated diarrhea includes grade 1 or 2 diarrhea with no other signs or symptoms. Management is conservative.

Complicated diarrhea includes grade 1 or 2 diarrhea with any one of the following risk factors:

• Moderate to severe cramping.
• Grade 2 or higher nausea/vomiting (see Table 1 in Nausea and Vomiting).
• Decreased performance status.
• Fever.
• Sepsis.
• Neutropenia.
• Frank bleeding.
• Dehydration.

Grade 3 or 4 diarrhea is also classified as complicated. Thorough evaluation and close monitoring is warranted.[44]

The time course of diarrhea and concomitant symptom development are key to determining the underlying etiology.[42] Medication and dietary intake, as well as a history of recent travel, may provide additional clues. Weight loss and reduced urine output provide additional data regarding the severity of the effects of diarrhea.

The goal of physical examination is to identify potential causes of diarrhea and its complications as quickly as possible to reduce morbidity. The physical examination includes vital signs and evaluation of skin turgor and oral mucosa to assess hemodynamic status and dehydration. Abdominal examination includes evaluation for rebound tenderness, guarding, hypoactive or hyperactive bowel sounds, and stool collection. A rectal exam can rule out fecal impaction but is performed judiciously in neutropenic or thrombocytopenic patients.[18]

Laboratory tests may include the following:[18]

• Stool cultures for bacterial, fungal, and viral pathogens.
• A complete chemistry panel and hematologic profile. This will provide information regarding the effect of diarrhea on kidney function and electrolytes and identify changes in white blood cell count in response to infection.
• Urinalysis with specific gravity to provide information regarding hydration status.
• Stool osmolality may also be measured.

In some cases, radiographic procedures are conducted to identify ileus, obstruction, or other abnormalities. In rare cases, endoscopy may be indicated.

Management of Diarrhea

A review analyzed early toxic deaths in two NCI-sponsored cooperative trials of irinotecan plus high-dose fluorouracil and leucovorin for advanced colorectal cancer. It led to the revision of clinical practice guidelines for the treatment of cancer treatment–induced diarrhea, with a heightened emphasis on assessment and early aggressive interventions. The guidelines distinguish between uncomplicated and complicated diarrhea.[44]

Uncomplicated diarrhea

The treatment of cancer-related diarrhea is often empiric and nonspecific. Whenever possible, treat underlying causes such as fecal impaction or modify the stimulant laxative regimen as necessary. Medications such as bulk laxatives and promotility agents (e.g., metoclopramide) are discontinued. Dietary changes are commonly made to stop or lessen the severity of cancer treatment–related diarrhea.[10,22,45] In some cases, these changes include advising patients to eat small, frequent meals and avoid the following:[46]

• Lactose-containing foods and beverages (milk and dairy products).
• Spicy foods.
• Alcohol.
• Caffeine-containing foods and beverages.
• Certain fruit juices.
• Gas-forming foods and beverages.
• High-fiber foods.
• High-fat foods.

When experiencing diarrhea, patients are encouraged to increase their intake of clear liquids to at least 3 L per day (e.g., water, sports drinks, broth, weak decaffeinated teas, caffeine-free soft drinks, clear juices, and gelatin).[15,47] For more information, see the Behavioral strategies for symptom management section in Nutrition in Cancer Care.

Some case reports suggest the efficacy of glutamine in relieving diarrhea and other gastrointestinal symptoms associated with cancer therapy. However, a randomized controlled trial that used oral glutamine to prevent pelvic radiation-induced diarrhea did not show any benefit.[48][Level of evidence: I][49,50]

Pharmacological therapy

The goals of pharmacological therapy include inhibition of intestinal motility, reduction in intestinal secretions, and promotion of absorption. Absorbents include agents that form a gelatinous mass that gives density to fecal material. Methylcellulose and pectin are most commonly used, but little data support their efficacy. Some patients may not tolerate these bulk-forming agents because of the large volume required for therapeutic effect and the associated abdominal discomfort and bloating. Adsorbents such as kaolin, clays, and activated charcoals have been used extensively, but no data support their use. Furthermore, they may inhibit absorption of other oral antidiarrheals.

Opioids bind to receptors within the gastrointestinal tract and reduce diarrhea by reducing transit time. Loperamide is the most common opioid used, due to its availability and reduced effect on cognition, although codeine and other opioids can also be effective.[42] Common loperamide doses begin with 4 mg, followed by 2 mg after each unformed stool, with a maximum of approximately 12 mg/day.[18,42] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[51][Level of evidence: I]

Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include the following:

• Aspirin may be useful for radiation-induced diarrhea.
• Bismuth subsalicylate is believed to have direct antimicrobial effects on Escherichia coli, so it is used to prevent traveler's diarrhea. This agent is contraindicated in patients who should not take aspirin, and large doses can produce toxic salicylate levels.
• Corticosteroids reduce edema associated with bowel obstruction and radiation colitis and can reduce the hormonal influences of some endocrine tumors.
• Octreotide.

Other pharmacological therapies for the relief of diarrhea may be specific to the underlying mechanism. Delayed diarrhea (>24 hours) occurs with irinotecan. In a small study, six of seven patients obtained relief with oral neomycin (1,000 mg three times daily). This relief occurred without reduction in the active metabolite of irinotecan, SN-38. Thus, the poorly metabolized antibiotic did not alter the efficacy of the chemotherapeutic agent.[52][Level of evidence: II] In another small study, 37 patients with non-small cell lung cancer received irinotecan. Investigators alkalized the patients' feces through oral administration of sodium bicarbonate, basic water, and ursodeoxycholic acid, while speeding transit time of the drug metabolites (thought to reduce damage to the intestinal lumen by reducing stasis of the drug) using magnesium oxide. The incidence of delayed diarrhea was significantly reduced in this group when compared with 32 patients who received the same chemotherapeutic regimen without oral alkalization and controlled defecation.[53][Level of evidence: III]

In addition to antidiarrheal agents and immunosuppressive medications, a specialized, five-phase dietary regimen may be started to effectively manage diarrhea associated with GVHD:[22]

1. Phase 1 consists of total bowel rest until diarrhea is reduced. Nitrogen losses associated with diarrhea can be severe and are compounded by the high-dose corticosteroids used to treat GVHD.
2. Phase 2 reintroduces oral feedings consisting of beverages that are isotonic, low residue, and lactose free to compensate for the loss of intestinal enzymes secondary to alterations in the intestinal villi and mucosa.
3. If the beverages in phase 2 are well tolerated, phase 3 may reintroduce solids containing minimal lactose, low fiber, low fat, low total acidity, and no gastric irritants.
4. In phase 4, dietary restrictions are progressively reduced as foods are gradually reintroduced and tolerance is established.
5. Phase 5 includes resumption of the patient's regular diet; however, most patients usually remain lactose intolerant.

Probiotics

Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and, upon administration, confer a benefit to the patient.[54] The use of probiotic functional foods (beneficial live microorganisms) to modify gut microflora has been suggested in clinical conditions associated with diarrhea, gut-barrier dysfunction, and inflammatory response.[55] There are a vast number of different strains of probiotics; however, much of the clinical research has investigated species belonging to the families of Lactobacillus and Bifidobacterium. Probiotics have been promoted for the following:[56,57,58,59,60,61,62][Level of evidence: I]

• Prevention of antibiotic-induced diarrhea and rotavirus.
• Treatment or prevention of inflammatory bowel disease, irritable bowel syndrome, and gastroenteritis.
• Treatment of necrotizing enterocolitis in premature infants.

In a double-blind, randomized, controlled trial, 450 adults with cancer who were receiving radiation to the pelvic region were randomly assigned to receive the blend probiotic product VSL #3 or placebo during radiation therapy. The authors reported a decrease in the incidence and severity of diarrhea. No adverse events were reported.[63]

Complicated diarrhea

Patients with complicated diarrhea may require further evaluation and more aggressive management. When patients are receiving chemotherapy, additional evaluation includes stool testing (including blood, fecal leukocytes, C. difficile, Salmonella, E. coli, Campylobacter, and infectious colitis), complete blood count, and electrolyte profile.[44] This workup and treatment is also considered for patients who progress to grade 3 or 4 diarrhea while taking loperamide.

The patient's symptoms will determine the level of care and type of treatments. A panel of experts suggested that severe radiation therapy–induced diarrhea may not require hospitalization. An alternative outpatient unit or intensive home care nursing may be able to provide the same level of care and monitoring.[44] The same panel recommended intravenous fluids, subcutaneous octreotide, and antibiotics for complicated diarrhea. While the optimal dose of octreotide has not been determined, octreotide may be started at a dose of 100 to 150 μg subcutaneously (SC) three times a day or 25 to 50 μg/hour intravenously (IV) with a dose escalation to 500 μg three times a day. This regimen continues until the patient has been diarrhea free for 24 hours.[44]

Octreotide, a somatostatin analogue, is currently the most promising agent in the management of severe diarrhea caused by a variety of diseases and treatments. The doses used in clinical trials have varied widely, and there is no consensus regarding optimal dose. Nevertheless, octreotide has been shown to be effective in relieving diarrhea associated with AIDS, carcinoid syndrome, and vasoactive intestinal polypeptide tumors.[64][Level of evidence: II][19]

Several open-label and randomized controlled studies of octreotide for chemotherapy-induced diarrhea have demonstrated the efficacy of this therapy.[65,66,67][Level of evidence: I];[68,69,70][Level of evidence: II] In a prospective trial of 32 patients who had chemotherapy-induced diarrhea that was refractory to loperamide, octreotide 100 µg SC three times a day produced complete resolution in 30 patients. Resolution occurred rapidly, with 5 patients responding within 24 hours after beginning treatment, 14 patients responding within 48 hours, and 11 patients responding within 72 hours. No adverse effects were noted.[71] Octreotide has also been shown to be effective for treating diarrhea associated with GVHD.[72,73]

An expert panel recommended using high-dose loperamide (2 mg q2h) for the first day of chemotherapy-induced, low-grade diarrhea (grade 1 or 2), followed by octreotide (100 µg–150 µg q8h).[42] If the patient presents with severe diarrhea (grade 3 or 4), octreotide (500 μg–1,500 µg SC or IV q8h) may be given as first-line therapy. A phase III, double-blind study of depot octreotide for the prevention of diarrhea during pelvic radiation treatment did not show any benefit.[74] In fact, some gastrointestinal symptoms, such as cramping, may have been worse. Parenteral hydration and electrolyte supplementation may be indicated, and in severe cases, total parenteral nutrition may be initiated. For more information, see Nutrition in Cancer Care.

Unique scenarios

Irinotecan

Irinotecan is notorious for causing diarrhea. Irinotecan is associated with both acute diarrhea (occurring immediately after drug administration) and delayed diarrhea (occurring more than 24 hours after drug administration). Acute diarrhea is related to acute cholinergic excess and responds well to atropine. Delayed diarrhea, however, is typically managed with antidiarrheals and other supportive measures, as outlined above.[1]

Immune checkpoint inhibitors

Immune-mediated colitis is a potential side effect of ICIs. CTLA-4 inhibitors typically cause diarrhea and colitis more frequently than PD-1 and PD-L1 inhibitors, with the highest rates of colitis seen in patients receiving a combination of ICIs.[75] The onset of these events can be unpredictable, but they typically occur within the first ten doses of an ICI and may occur after cessation of an ICI.[76] Symptoms are treated according to the grade of diarrhea/colitis. Patients with mild diarrhea/colitis may be managed symptomatically with fluids and antidiarrheals. More severe diarrhea/colitis may necessitate treatment with systemic steroids and even permanent discontinuation of ICI therapy. Detailed management of ICI-induced diarrhea is further outlined in National Comprehensive Cancer Network guidelines for the management of immunotherapy-related toxicities.[77]

Phosphatidylinositol 3-kinase (PI3K) inhibitors

The U.S. Food and Drug Administration has approved four PI3K inhibitors, two of which (idelalisib and duvelisib) carry a boxed warning for gastrointestinal complications, including diarrhea.[78,79] Given the severity of diarrhea that may be seen with idelalisib, an expert panel convened to develop management strategies for idelalisib-associated diarrhea.[80] Panelists commented that it is not clear whether diarrhea is a class effect of PI3K inhibitors. The authors noted that for idelalisib, two types of diarrhea may be seen. The first type appears to be self-limiting, occurring within the first 8 weeks of treatment. The second type tends to respond poorly to antidiarrheal therapy and occurs later, approximately 7 months after the start of treatment. In the second type of diarrhea, the histological appearance of the colon is consistent with lymphocytic colitis. In this case, the panel recommended considering treatment with steroids or budesonide.[80]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

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23. DuPont HL: Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 92 (11): 1962-75, 1997.
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25. Iacovelli R, Pietrantonio F, Palazzo A, et al.: Incidence and relative risk of grade 3 and 4 diarrhoea in patients treated with capecitabine or 5-fluorouracil: a meta-analysis of published trials. Br J Clin Pharmacol 78 (6): 1228-37, 2014.
26. NDA 20-954 Busulfex (busulfan) Injection. Minnetonka, Minn.: Orphan Medical, Inc., 1999. Available online. Last accessed Aug. 24, 2023.
27. Murthy RK, Loi S, Okines A, et al.: Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 382 (7): 597-609, 2020.
28. Curigliano G, Mueller V, Borges V, et al.: Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol 33 (3): 321-329, 2022.
29. Leboulleux S, Bastholt L, Krause T, et al.: Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol 13 (9): 897-905, 2012.
30. Wells SA, Robinson BG, Gagel RF, et al.: Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 30 (2): 134-41, 2012.
31. Fowler NH, Samaniego F, Jurczak W, et al.: Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol 39 (15): 1609-1618, 2021.
32. Kim YH, Bagot M, Pinter-Brown L, et al.: Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol 19 (9): 1192-1204, 2018.
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34. Hong DS, Fakih MG, Strickler JH, et al.: KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med 383 (13): 1207-1217, 2020.
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36. Gounder MM, Razak AA, Somaiah N, et al.: Selinexor in Advanced, Metastatic Dedifferentiated Liposarcoma: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Oncol 40 (22): 2479-2490, 2022.
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39. Escudier B, Eisen T, Stadler WM, et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356 (2): 125-34, 2007.
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41. Llovet JM, Ricci S, Mazzaferro V, et al.: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359 (4): 378-90, 2008.
42. Kornblau S, Benson AB, Catalano R, et al.: Management of cancer treatment-related diarrhea. Issues and therapeutic strategies. J Pain Symptom Manage 19 (2): 118-29, 2000.
43. Mertz HR, Beck CK, Dixon W, et al.: Validation of a new measure of diarrhea. Dig Dis Sci 40 (9): 1873-82, 1995.
44. Benson AB, Ajani JA, Catalano RB, et al.: Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22 (14): 2918-26, 2004.
45. Polisena CG: Nutrition concerns with the radiation therapy patient. In: McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. The American Dietetic Association, 2000, pp 70-8.
46. McCallum PD, Polisena CG, eds.: The Clinical Guide to Oncology Nutrition. The American Dietetic Association, 2000.
47. Hogan CM: The nurse's role in diarrhea management. Oncol Nurs Forum 25 (5): 879-86, 1998.
48. Kozelsky TF, Meyers GE, Sloan JA, et al.: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 21 (9): 1669-74, 2003.
49. Savy GK: Glutamine supplementation. Heal the gut, help the patient. J Infus Nurs 25 (1): 65-9, 2002 Jan-Feb.
50. Ziegler TR, Bye RL, Persinger RL, et al.: Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 315 (1): 4-10, 1998.
51. Cascinu S, Bichisao E, Amadori D, et al.: High-dose loperamide in the treatment of 5-fluorouracil-induced diarrhea in colorectal cancer patients. Support Care Cancer 8 (1): 65-7, 2000.
52. Kehrer DF, Sparreboom A, Verweij J, et al.: Modulation of irinotecan-induced diarrhea by cotreatment with neomycin in cancer patients. Clin Cancer Res 7 (5): 1136-41, 2001.
53. Takeda Y, Kobayashi K, Akiyama Y, et al.: Prevention of irinotecan (CPT-11)-induced diarrhea by oral alkalization combined with control of defecation in cancer patients. Int J Cancer 92 (2): 269-75, 2001.
54. de Vrese M, Schrezenmeir J: Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111: 1-66, 2008.
55. Isolauri E: Probiotics in human disease. Am J Clin Nutr 73 (6): 1142S-1146S, 2001.
56. Johnston BC, Supina AL, Ospina M, et al.: Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev (2): CD004827, 2007.
57. Pillai A, Nelson R: Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev (1): CD004611, 2008.
58. Huertas-Ceballos A, Logan S, Bennett C, et al.: Dietary interventions for recurrent abdominal pain (RAP) and irritable bowel syndrome (IBS) in childhood. Cochrane Database Syst Rev (1): CD003019, 2008.
59. Alfaleh K, Bassler D: Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev (1): CD005496, 2008.
60. Karimi O, Peña AS: Indications and challenges of probiotics, prebiotics, and synbiotics in the management of arthralgias and spondyloarthropathies in inflammatory bowel disease. J Clin Gastroenterol 42 (Suppl 3 Pt 1): S136-41, 2008.
61. Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev (3): CD006634, 2008.
62. Eghbali A, Ghaffari K, Khalilpour A, et al.: The effects of LactoCare synbiotic administration on chemotherapy-induced nausea, vomiting, diarrhea, and constipation in children with ALL: A double-blind randomized clinical trial. Pediatr Blood Cancer 70 (6): e30328, 2023.
63. Delia P, Sansotta G, Donato V, et al.: Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 13 (6): 912-5, 2007.
64. Cello JP, Grendell JH, Basuk P, et al.: Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial. Ann Intern Med 115 (9): 705-10, 1991.
65. Cascinu S, Fedeli A, Fedeli SL, et al.: Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial. J Clin Oncol 11 (1): 148-51, 1993.
66. Cascinu S, Fedeli A, Fedeli SL, et al.: Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin. Oncology 51 (1): 70-3, 1994 Jan-Feb.
67. Gebbia V, Carreca I, Testa A, et al.: Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy. Anticancer Drugs 4 (4): 443-5, 1993.
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69. Wadler S, Haynes H, Wiernik PH: Phase I trial of the somatostatin analog octreotide acetate in the treatment of fluoropyrimidine-induced diarrhea. J Clin Oncol 13 (1): 222-6, 1995.
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73. Morton AJ, Durrant ST: Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation. Clin Transplant 9 (3 Pt 1): 205-8, 1995.
74. Martenson JA, Halyard MY, Sloan JA, et al.: Phase III, double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea in patients receiving pelvic radiation therapy: results of North Central Cancer Treatment Group N00CA. J Clin Oncol 26 (32): 5248-53, 2008.
75. Tandon P, Bourassa-Blanchette S, Bishay K, et al.: The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis. J Immunother 41 (3): 101-108, 2018.
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Radiation Enteritis

Causes of Radiation Enteritis

Almost all patients undergoing radiation to the abdomen, pelvis, or rectum will show signs of acute enteritis. Injuries are clinically evident during or within 3 months after irradiation, with the greatest prevalence during the fourth and fifth weeks.[1] Chronic radiation enteritis may present months to years after the completion of therapy, or it may begin as acute enteritis and persist after treatment ends. Only 10% to 20% of people treated with radiation to the abdomen develop chronic problems.[2]

The large and small bowel are sensitive to ionizing radiation. Although the probability of tumor control increases with the radiation dose, so does the damage to normal tissues. Acute side effects to the intestines occur with an exposure of approximately 10 Gy. Because curative radiation doses for many abdominal or pelvic tumors range between 25 and 76 Gy, enteritis is likely to occur.[2]

Factors that influence the occurrence and severity of radiation enteritis include the following:[2]

• Dose and fractionation of radiation.
• Modality of radiation.
• Tumor size and extent.
• Volume of normal bowel treated.
• Concomitant chemotherapy.
• Individual patient variables (e.g., previous abdominal or pelvic surgery, hypertension, diabetes mellitus, smoking, inadequate nutrition).

In general, the higher the daily and total dose delivered to the normal bowel and the greater the volume of normal bowel treated, the greater the risk of radiation enteritis. In addition, the individual patient variables listed above can decrease vascular flow to the bowel wall and impair bowel motility, increasing the chance of radiation injury.

Acute Radiation Enteritis

Diagnosis of acute radiation enteritis

Radiation therapy exerts a cytotoxic effect mainly on rapidly proliferating epithelial cells, like those lining the large and small bowel. Crypt cell wall necrosis can be observed 12 to 24 hours after a daily dose of 1.5 to 3 Gy.[3] Progressive loss of cells, villous atrophy, and cystic crypt dilation occur in the ensuing days and weeks. Patients suffering from acute enteritis may complain of nausea, vomiting, abdominal cramping, tenesmus, and watery diarrhea.[1,2] With diarrhea, the digestive and absorptive functions of the gastrointestinal tract are altered or lost, resulting in malabsorption of fat, lactose, bile salts, and vitamin B₁₂. Symptoms of proctitis—including mucoid rectal discharge, rectal pain, and rectal bleeding (if mucosal ulceration is present)—may result from radiation damage to the anus or rectum.

One study of radiation for lung and head and neck cancers, with or without chemotherapy, noted significant diarrhea despite no direct radiation to the large or small intestine. Higher rates were noted for chemoradiation (42%) than for radiation alone (29%). Additionally, this radiation-induced diarrhea was associated with worse health outcomes and increased resource utilization. Individuals with moderate or severe diarrhea were more likely to have a gastrostomy tube placement, weight loss, unplanned office visits, more inpatient days, and longer radiation breaks. This early report requires additional validation studies to fully evaluate the prevalence and impact of this phenomenon.[4]

Acute enteritis occurs during or within 3 months after irradiation, with the greatest prevalence during the fourth and fifth weeks. Acute enteritis symptoms usually resolve 2 to 3 weeks after the completion of treatment, and the mucosa may appear nearly normal.[1]

Management of acute radiation enteritis

Medical management includes treating diarrhea, dehydration, malabsorption, and abdominal or rectal discomfort. Symptoms usually resolve with medications, dietary changes, and rest. If symptoms become severe despite these measures, a treatment break may be warranted.

Medications may include the following:[1,5]

• Loperamide hydrochloride, a synthetic antidiarrheal agent. Recommended initial dose: Two capsules (4 mg) by mouth every 4 hours, followed by one capsule (2 mg) by mouth after each unformed stool. Daily total dose should not exceed 16 mg (eight capsules).
• Cholestyramine, a bile salt sequestering agent. Dose: One package by mouth after each meal and at bedtime.
• Antibiotics.
• Pentoxifylline.
• Tocopherol.
• Steroids.
• Probiotics.

The role of nutrition

Damage to the intestinal villi from radiation therapy results in a reduction or loss of enzymes, such as lactase. Lactase is essential in the digestion of milk and milk products. Although there is no evidence that a lactose-restricted diet will prevent radiation enteritis, a diet that is lactose free, low fat, and low residue can help manage symptoms.[6][Level of evidence: I]

Foods to avoid

• Milk and milk products. Exceptions are buttermilk and yogurt, which are often tolerated because lactose is altered by the presence of Lactobacillus. Processed cheese may also be tolerated because the lactose is removed with the whey when it is separated from the cheese curd. Milkshake supplements such as Ensure are lactose free and may be used.
• Whole-bran bread and cereal.
• Nuts, seeds, and coconuts.
• Fried, greasy, or fatty foods.
• Fresh and dried fruit and some fruit juices such as prune juice.
• Raw vegetables.
• Rich pastries.
• Popcorn, potato chips, and pretzels.
• Strong spices and herbs.
• Chocolate, coffee, tea, and soft drinks with caffeine.
• Alcohol and tobacco.

Foods to encourage

• Fish, poultry, and meat that are cooked, broiled, or roasted.
• Bananas, applesauce, peeled apples, and apple and grape juices.
• White bread and toast.
• Macaroni and noodles.
• Baked, boiled, or mashed potatoes.
• Cooked vegetables that are mild, such as asparagus tips, green and waxed beans, carrots, spinach, and squash.
• Mild processed cheese, eggs, smooth peanut butter, buttermilk, and yogurt.

Helpful hints

• Ingest food at room temperature.[7]
• Drink 3,000 cc of fluid per day. Allow carbonated beverages to lose carbonation before being ingested.
• Add nutmeg to food, which helps decrease mobility of the gastrointestinal tract.
• Start a low-residue diet on day 1 of radiation therapy treatment.[Level of evidence: IV]

Chronic Radiation Enteritis

Diagnosis of chronic radiation enteritis

Only 10% to 20% of patients who receive abdominal or pelvic irradiation develop chronic radiation enteritis. Signs and symptoms include the following:[2]

• Colicky abdominal pain.
• Bloody diarrhea.
• Steatorrhea.
• Weight loss.
• Nausea and vomiting.

Less common symptoms are bowel obstruction, fistulas, bowel perforation, and massive rectal bleeding.

The initial signs and symptoms occur 6 to 18 months after radiation therapy. Radiological findings include submucosal thickening, single or multiple stenoses, adhesions, and sinus or fistula formation.[8] Microscopic findings include villi that are fibrotic or may be lost altogether. Ulceration is common, varying from simple loss of epithelial layers to ulcers that may penetrate to different depths of the intestinal wall, even to the serosa. Lymphatic tissue is often atrophic or absent. The submucosa is severely diseased. Arterioles and small arteries show profound changes, with hyalinization of the entire wall thickness. The muscularis is often distorted or focally replaced by fibrosis.

The diagnosis of chronic radiation enteritis may be difficult to make. Clinically and radiologically recurrent tumor needs to be ruled out. Because of the possible latency of the illness, it is essential to obtain a detailed history of the patient's radiation therapy course. It is often advisable to include the radiation therapy physician in managing the patient's care.

Treatment of chronic radiation enteritis

Medical management of the patient's symptoms (which are similar to symptoms of acute radiation enteritis) is indicated, with surgical management reserved for severe damage.[6][Level of evidence: I]

The timing and choice of surgical techniques remain somewhat controversial. A lower operative mortality rate (21% vs. 10%) and incidence of anatomic dehiscence (36% vs. 6%) have been reported with intestinal bypass compared with resection.[9][Level of evidence: II][10] Clinicians who favor resection point out that the removal of diseased bowel decreases the mortality rate for resection and is comparable to the bypass procedure.[9] All agree that simple lysis of adhesions is inadequate and that fistulas require bypass.

Surgery is undertaken only after careful assessment of the patient's clinical condition and extent of radiation damage. Wound healing is often delayed, necessitating prolonged parenteral feeding after surgery. Even after apparently successful operations, symptoms may persist in a significant share of patients.[11]

Prevention of chronic radiation enteritis

Treatment techniques that can minimize the risk of severe radiation enteritis include the following:

1. Radiation therapy techniques:
   1. Use of a three- or four-field technique (as opposed to a two-field technique) to minimize the amount of small bowel exposed to treatment.
   2. Treatment of the patient in a physical position that will aid in removing as much small bowel from the treatment field as possible (e.g., treating a patient with a full bladder each day to aid in pushing the small bowel up and out of the pelvis when pelvic radiation is given).
   3. Daily treatment of all fields, resulting in a lower integral dose and more homogenous dose distribution.
   4. Use of computerized radiation dosimetry to best design the treatment plan and use of high-energy treatment machines such as linear accelerators that deliver a high dose-to-tumor volume while sparing normal structures.[12]
2. Surgery. Placing clips in high-risk areas to better define the location or former location of the tumor and aid in radiation treatment planning.
3. Modification of treatment sequencing. An area for exploration is the sequencing of radiation, chemotherapy, and surgery and its influence on the severity of enteritis.

References:

1. Harb AH, Abou Fadel C, Sharara AI: Radiation enteritis. Curr Gastroenterol Rep 16 (5): 383, 2014.
2. Loge L, Florescu C, Alves A, et al.: Radiation enteritis: Diagnostic and therapeutic issues. J Visc Surg 157 (6): 475-485, 2020.
3. Gusev IA, Guskova AK, Mettler FA: Medical Management of Radiation Accidents. 2nd ed. CRC Press/Taylor & Francis Group, 2001. Also available online. Last accessed May 6, 2023.
4. Sonis S, Elting L, Keefe D, et al.: Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. Support Care Cancer 23 (2): 433-9, 2015.
5. Hille A, Christiansen H, Pradier O, et al.: Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis. Strahlenther Onkol 181 (9): 606-14, 2005.
6. Stryker JA, Bartholomew M: Failure of lactose-restricted diets to prevent radiation-induced diarrhea in patients undergoing whole pelvis irradiation. Int J Radiat Oncol Biol Phys 12 (5): 789-92, 1986.
7. Yasko JM: Care of the Client Receiving External Radiation Therapy. Reston Publishing Company, Inc., 1982.
8. Mendelson RM, Nolan DJ: The radiological features of chronic radiation enteritis. Clin Radiol 36 (2): 141-8, 1985.
9. Lillemoe KD, Brigham RA, Harmon JW, et al.: Surgical management of small-bowel radiation enteritis. Arch Surg 118 (8): 905-7, 1983.
10. Wobbes T, Verschueren RC, Lubbers EJ, et al.: Surgical aspects of radiation enteritis of the small bowel. Dis Colon Rectum 27 (2): 89-92, 1984.
11. Wellwood JM, Jackson BT: The intestinal complications of radiotherapy. Br J Surg 60 (10): 814-8, 1973.
12. Minsky BD, Cohen AM: Minimizing the toxicity of pelvic radiation therapy in rectal cancer. Oncology (Huntingt) 2 (8): 21-5, 28-9, 1988.

Changes to This Summary (08 / 24 / 2023)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Diarrhea

Added Eghbali et al. as reference 62.

This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of gastrointestinal complications, including constipation, impaction, bowel obstruction, diarrhea, and radiation enteritis. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

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• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Gastrointestinal Complications are:

• Alison Palumbo, PharmD, MPH, BCOP (Oregon Health and Science University Hospital)
• Maria Petzel, RD, CSO, LD, CNSC, FAND (University of TX MD Anderson Cancer Center)
• Megan Reimann, PharmD, BCOP (Total CME)

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Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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PDQ® Supportive and Palliative Care Editorial Board. PDQ Gastrointestinal Complications. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/constipation/GI-complications-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389211]

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Last Revised: 2023-08-24