Chemotherapy-Induced Diarrhea
Quick Facts
- Chemotherapy-induced diarrhea results from mechanical and biochemical disturbances from effects of chemotherapy on the bowel mucosa
- Diarrhea occurs in 6% of hospitalized patients with cancer, up to 10% of patients with advanced cancer, 20% to 49% of patients undergoing abdominopelvic irradiation, 50% to 87% of patients receiving fluoropyrimidines (5-fluorouracil [5-FU]) and topoisome
- The 5 types of diarrhea are osmotic, secretory, exudative, malabsorptive, and dysmotility-associated
- Download Presentation
Background
Diarrhea, a common symptom among patients with colorectal cancer (CRC), is characterized by frequent, watery stools, impairs quality of life, can lead to other complications, and may even be life threatening. Diarrhea occurs in 6% of hospitalized patients with cancer, up to 10% of patients with advanced cancer, 20% to 49% of patients undergoing abdominopelvic irradiation, 50% to 87% of patients receiving fluoropyrimidines (5-fluorouracil [5-FU]) and topoisomerase inhibitors (irinotecan), and in 80% of patients with carcinoid tumors.1
Diarrhea can be classified into 5 categories2:
- Osmotic diarrhea is related to mechanical disturbances resulting from ingestion of hyperosmolar substances such as sorbitol or enteral feeding solutions (J-tubes, G-tubes). This type of diarrhea is watery and voluminous and resolves when the causative agent is withdrawn.
- Secretory diarrhea is related to biochemical disturbances caused by enterotoxin-producing pathogens such as Clostridium difficile, Escherichia coli, and endocrine tumors, resulting in a mechanical response. This diarrhea is watery and voluminous.
- Exudative diarrhea is often caused by toxicity from radiation therapy to the bowel mucosa, resulting in mucosal atrophy and fibrosis. This diarrhea is characterized by a high frequency of stools (> 6 per day, with variable volume, although less than 1,000 mL/day). Stools are characterized by mucous and blood.
- Malabsorptive diarrhea is related to both mechanical and biochemical disturbances, which can result from enzyme deficiencies. Stools are voluminous, foul-smelling, and steatorrhea-type.
- Dysmotility-associated diarrhea is related to a mechanical disturbance or peristaltic dysfunction that results in rapid transit time of stool through the small and large intestine. Stools are small, with a semisolid/liquid consistency and variable volume and frequency.
Pathophysiology and Contributing Factors
Gastrointestinal motility involves processes that promote the absorption of nutrients. Movement through the gastrointestinal tract requires coordination of intraluminal pressure and smooth muscle contractions controlled by the enteric nervous system and peptide hormonal release. Diarrhea is caused by an imbalance in the physiologic mechanisms of the gastrointestinal tract and is the result of impaired absorption and excessive secretion. Chemotherapy-induced diarrhea is caused by mechanical and biochemical disturbances resulting from the effects of chemotherapy on the bowel mucosa. Stools are watery or semisolid. In radiation that involves the abdomen and/or pelvis and chemotherapy-induced diarrhea, acute damage to the epithelial crypt cells results in necrosis, inflammation, and ulceration of the intestinal mucosa. Atrophy and fibrosis of the lining can occur over time, resulting in decreased absorption of water and electrolytes, producing diarrhea.3
Decreased absorption of fluid and electrolytes can result from the presence of osmotically active substances in the lumen and/or increased intestinal motility. Increased secretion of fluid and electrolytes can result from endogenous secretagogues and/or exogenous toxins.4
Many factors can contribute to cancer treatment–induced diarrhea (CTID). For patients receiving chemotherapy, a history of diarrhea with previous chemotherapy can place them at risk. Some chemotherapeutic agents used in the treatment of CRC have been identified as causing CTID, including fluoropyrimidines (5-FU, capecitabine [prodrug of 5-FU]), topoisomerase I inhibitors (irinotecan),5 and the biologic agents cetuximab6 and panitumumab.7 For patients receiving radiation therapy (RT), the incidence of diarrhea depends on several factors: total RT dose, size of the RT field, site being irradiated, and dose per fraction.3
Assessment
A detailed assessment is imperative to appropriate management of CTID. A hallmark assessment tool is patient report, which should incorporate a description of baseline bowel movements and current bowel movement history from onset, including frequency, volume, and consistency of stool, incontinence, presence of blood, or distinct change in odor of stool.8
The US Department of Health and Human Services, National Institutes of Health, and the National Cancer Institute have outlined a grading system for adverse events to assist in categorizing the severity of the event. The grading system spans from 1 through 5 based on patient assessment (Table 1).9
Table 1
|
Grade 1
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
Patients with or without ostomy
|
Increase of < 4 stools per day over baseline, mild increase in ostomy output compared with baseline
|
Increase of 4-6 stools per day over baseline, IV fluids indicated < 24 hours, moderate increase in ostomy output compared with baseline, not interfering with ADL
|
Increase of = 7 stools per day over baseline, incontinence, IV fluids = 24 hours, hospitalization, severe increase in ostomy output compared with baseline, interfering with ADL
|
Life-threatening consequences (eg, hemodynamic collapse)
|
Death
|
ADL = activities of daily living.
Patients should also be evaluated for associated symptoms of bloating, abdominal cramping, fever or nausea, and vomiting. Additionally, it is important to assess for secondary effects, such as signs and symptoms of dehydration, including orthostatic hypotension, dry mouth, excessive thirst, dizziness, feelings of weakness, decreased urination, or weight loss.10 A comprehensive physical examination, including thorough examination of the abdomen, should incorporate palpation for tenderness or distension and percussion for dullness, which may indicate obstruction and auscultation for bowel sounds.
Pharmacologic Interventions
Antidiarrheal agents are divided into 4 categories based on mechanism of action (Table 2).1,10
Table 2
Drug Class
|
Drug
|
Dose
|
Dose Limit/
Duration
|
Opioid
|
Lomotil(2.5 mg diphenoxylate with 0.025mg atropine sulfate/tablet)
Opium tincture(10% opium liquid: 10 mg morphine/mL with 19% alcohol)
Codeine
Paregoric(0.4 mg morphine/mL)
|
May load with 2tablets, then 1-2 tablets 4 times a day
0.3-1 mL PO every 2-6 hours until controlled
15-60 mg PO every 4-6 hours as needed
5-10 mL PO 1-4 times a day
|
Not to exceed 8tablets/day
Not to exceed 6mL/24 hours
|
Nonopioid
|
Imodium®(loperamide)
(2-mg capsules or liquid 1mg/mL or 1 mg/5 mL)
|
May load 4 mg orally then 2 mg after each loose stool
|
Not to exceed 16 mg/day
Discontinue after a 12-hour diarrhea-free interval
|
Absorbents
|
Bismuth subsalicylate (Pepto-Bismol®)(chewable tablets: 262 mg or suspensions 262 mg/15 mL or 524 mg/15 mL)
Kaopectate(5.85 g kaolin and 130 mg pectin/30 mL):
|
Dosing 524 mg every 30 minutes
2-6 g every 4 hours as needed
|
Not to exceed 5g/day
|
Somatostatin analogue
|
Octreotide acetate
|
100-150 mcg SC 3times a day
|
2nd-line treatment for loperamide-refractory CTID
|
Nonpharmacologic Interventions
Diet modifications:11
- Select foods that build stool consistency and that are low in fiber and contain pectin
- Bananas, applesauce, rice
- Eat foods high in potassium
- Peach and apricot nectar
- Boiled or mashed potatoes without skin
- Lactose-free milk
- Bananas
- Eat foods at room temperature to minimize peristalsis
- Maintain a lactose-free diet if indicated
- Avoid milk and dairy products
- May use lactose-free dairy products or soy milk products
- Increase fluid intake to at least 3 liters per day and avoid alcohol and carbonated beverages
- Bouillon
- Fruitades
- Gatorade®, Propel®, or other sports drinks
- Pedialyte® or Pedialyte® ice pops
- Ice pops
- Gelatin
- Avoid high-fiber, high-fat, greasy, or spicy foods or caffeine-containing foods
- Whole-grain breads or cereals
- Raw vegetables
- Nuts
- Seeds
- Popcorn
- Relishes or pickles
- High-fat spreads or dressings
- Chocolate
- Coffee/tea
- Cola drinks
Follow-up
Patients experiencing persistent diarrhea for > 24 hours despite appropriate intervention strategies should be evaluated further with laboratory and diagnostic tests. This workup should include complete blood count, examination of stool for occult blood, metabolic panel to assess electrolyte levels, BUN/creatinine, albumin, stool cultures for enteric pathogens, C difficile, and ova and parasites, and a flat plate of the abdomen or obstruction series (as indicated by history and physical examination).1 An algorithm of assessment and management strategies follows in Table 3.
- Have patient or caregiver record number and consistency of stools
- Call doctor or nurse if diarrhea persists in frequency and volume for > 24 hours after following outlined plan of care
Table 3
Assessment
- Hallmark assessment tool is patient report and should
- Description of baseline bowel movements and current bowel movements
- Onset and frequency of diarrhea
- Volume and consistency of stool incontinence
- Presence of blood or distinct change in color or odor of stool
- Assess patient for fever, dizziness, abdominal pain/cramping, or weakness
- Review medication list to identify diarrheogenic agents
- Review food history to identify diarrhea-enhancing foods
|
Management of Chemotherapy-Induced Diarrhea
Grade or Occurrence of Diarrhea
|
Management and Patient Education
|
First 24 hours
|
Instruct patient to
- Avoid all lactose-containing products, alcohol, carbonated beverages, caffeine, and high-osmolar supplements
- Drink 8-10 glasses of liquids/day (bouillon, rehydrating drinks with electrolytes such as Gatorade)
- Follow the BRAT (bananas, rice, applesauce, and toast) diet
Pharmacologic intervention
·Begin loperamide 4 mg PO followed by 2mg every 4 hours (not to exceed 16 mg daily)
·Hold cytotoxic chemotherapy for³grade 2 diarrhea and consider dose reduction for subsequent cycles
If diarrhea resolves in 24 hours, instruct patient to
- Stop loperamide after a 12-hour diarrhea-free interval
- Slowly add solid foods, such as plain pasta, skinless white chicken, scrambled eggs, and other easily digestible foods
- Continue to avoid lactose-containing products for 1 week following resolution of diarrhea, because a transit loss of lactase activity may occur in the bowel, resulting in temporary lactose intolerance
- Avoid green, leafy vegetables
|
Grade 1-2 diarrhea persists 24-48 hours
|
- Increase loperamide to 2 mg every 2 hours and 4 mg every 4 hours during sleeping hours
- Initiate oral antibiotics, fluoroquinolones preferred
If diarrhea resolves in 24 hours, follow instructions in box above
|
Grade 1-2 diarrhea persists 48-72 hours
|
Begin evaluation with
- Physical examination of the abdomen
- Stool workup, including stool cultures for enteric pathogens,C difficile, and ova and parasites
- Laboratory data of complete blood count and electrolytes, including potassium
Interventions
- Fluid and electrolyte repletion
- Discontinue loperamide
- Begin 2nd-line agent
–Octreotide 100-150 mcg SC 3 times a day, with dose escalation to 500 mcg 3times a day
–Other 2nd-line agent
|
Grade 1-2 diarrhea progresses to grade 3-4 diarrhea, or patient develops symptoms associated with complicated diarrhea
|
Admit to the hospital for
- Stool evaluation
- Complete blood count and electrolyte panel
Interventions
- Fluid and electrolyte repletion
- Antibiotics
- Begin 2nd-line agents as above
- Hold cytotoxic chemotherapy and consider dose reduction for subsequent cycles
|
Grade 3 or 4 diarrhea or grade 1 or 2 with one or more of the following signs: cramping, nausea/vomiting (³grade 2), decreased performance status, fever, sepsis, neutropenia, bleeding, or dehydration
|
Admit to thehospital and follow above guidelines
|
Modified from Viale et al.10 Originally based on data from Benson et al.1
Typhlitis, also called necrotizing enterocolitis, is a rare complication of cancer therapy and can be life threatening if not recognized and treated emergently. Typhlitis may present as bloody diarrhea accompanied by right lower quadrant abdominal pain and fever. The pathogenesis of typhlitis generally requires mucosal injury by chemotherapy or other means (mucositis), altering gut flora and leaving the patient vulnerable to microorganism invasion of the gut and profound neutropenia.12 Several case reports have been published concerning CRC patients receiving therapy with 5-FU and leucovorin.13 Necrotizing enterocolitis has been reported in patients taking capecitabine, an oral fluoropyrimidine.14 Workup for necrotizing enterocolitis/typhlitis should include computed tomography of the abdomen and pelvis.
Clinical Practice Guidelines
National Cancer Institute (NCI)
Click here for a comprehensive review of all chemotherapy-induced gastrointestinal complications. Updated January 15, 2010. Accessed January 27, 2010.
Patient Care Management Protocols/Algorithms
Benson et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004;22:2918-2926. Page 2923 shows an algorithm for assessment and management of treatment-induced diarrhea (PDF) http://jco.ascopubs.org/content/vol22/issue14/images/large/zlj0100412800001.jpeg
Oncology Nursing Society (ONS)
ONS Putting Evidence into Practice®(PEP) clinical resource material for the assessment and management of diarrhea is available online athttp://www.ons.org/Research/PEP/Topics/Diarrhea. Accessed January 27, 2010.
References
- Benson AB III, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment–induced diarrhea. J Clin Oncol. 2004;22:2918-2926.
- Rutledge DN, Engelking C. Cancer-related diarrhea: selected findings of a national survey of oncology nurse experiences. Oncol Nurs Forum.1998;25:861-873.http://www.erbitux.com/erbitux/erb/home/index.jsp?BV_UseBVCookie=Yes. Accessed January 27, 2010.
- Gwede CK. Overview of radiation- and chemoradiation-induced diarrhea. Semin Oncol Nurs. 2003;19(4 suppl 3):6-10.
- Hogan CM. The nurse’s role in diarrhea management. Oncol Nurs Forum. 1998;25:879-886.
- Viele CS. Overview of chemotherapy-induced diarrhea [review]. Semin Oncol Nurs. 2003;19:2-5.
- Erbitux (cetuximab injection) prescribing information.
- Vectibix (panitumumab) prescribing information. http://www.vectibix.com/prescribing_information/prescribing_information.html. Accessed January 27, 2010. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.02_2009-09-15_QuickReference_8.5x11.pdf Accessed January 27, 2010.
- Kornblau S, Benson AB, Catalano R, et al. Management of cancer treatment-related diarrhea: issues and therapeutic strategies. J Pain Symptom Manage. 2000;19:118-129.
- National Cancer Institute. Common Terminology Criteria for Adverse Events v4.02. (CTCAE v4.02) page 13.
- Viale PH, Fung A, Zitella L. Advanced colorectal cancer: current treatment and nursing management with economic considerations. Clin J Oncol Nurs. 2005;9:541-552. Song LM, Marcon NE. UpToDate for Patients: necrotizing enterocolitis (typhlitis) in adults. http://www.uptodate.com/patients/content/topic.do?topicKey=gi_infec/13562&title=Necrotizing+enterocolitis; 2009. Accessed January 27, 2010.
- McCallum P, Polisena C, eds. The Clinical Guide to Oncology Nutrition. Chicago: American Dietetic Association; 2000.
-
- Hayes, D, Leonardo JM. Neutropenic enterocolitis in a woman treated with 5-fluorouracil and leucovorin in colon carcinoma. N C Med J. 2002:53:132-134.http://www.rocheusa.com/products/xeloda.%20Accessed Accessed January 27, 2010.
- Xeloda (capecitabine) tablets prescribing information.
Key Definitions
endogenous secretagogues—an internal substance that induces secretion from cells
exogenous toxin—a poisonous substance, especially a protein, that is produced by living cells or organisms outside the body and is capable of causing disease when introduced into the body tissues
steatorrhea—an excessive amount of fat in the feces that may result in loose, foul-smelling fecal material that floats
|