Diarrhea

Why does chemotherapy cause diarrhea?

Chemotherapy damages rapidly dividing cells. Cancer cells tend to divide rapidly and uncontrollably. However, some healthy cells also divide rapidly, such as those that line the interior of the digestive tract. Chemotherapy also damages these cells, leading to a disruption in the delicate fluid balance that they maintain. Specifically, absorption of fluid from the gastrointestinal (GI) tract back into the body is decreased, and secretion of fluid and electrolytes in the stool is increased. This causes watery bowel movements, the definition of diarrhea.

Why is it important to manage diarrhea?

Diarrhea is not only an inconvenient side effect of cancer treatment, but it can also:

• Be life threatening if not adequately managed
• Lead to dehydration, electrolyte imbalance, and low immune function
• Cause malnutrition due to reduced absorption of nutrients
• Cause pain and/or bleeding as a result of the increased frequency of bowel movements
• Create an opportunity for the entry of bacteria into your body

Diarrhea can be severe enough that you are unable to tolerate your prescribed chemotherapy treatments. Chemotherapy treatments are commonly delayed if diarrhea persists. A disruption or delay in treatment may diminish the effect of treatment.

What makes diarrhea worse?

Some factors may make chemotherapy-related diarrhea worse. For example, damage to the intestines as a result of surgery or radiation may make the GI system more susceptible to irritation. Medications such as antibiotics, diabetes, irritable bowel syndrome, reduced pancreas function, and other conditions may also worsen diarrhea. If you have certain biochemical characteristics, you may be more sensitive to chemotherapy drugs.

• Sensitivity to 5-FU -  Some individuals are more sensitive to 5-FU because they have significantly less of the enzyme that breaks down this drug. These individuals experience more side effects from treatment with 5-FU, including diarrhea, low white blood cell count, and mouth sores.
• Sensitivity to Camptosar^® (irinotecan) - Some individuals are more sensitive to the drug irinotecan due to a genetic disorder called Gilbert’s syndrome that limits their ability to remove the drug from their bodies. This syndrome is difficult to detect before administration of irinotecan. If you experience severe side effects after your first dose of irinotecan, Gilbert’s syndrome may be the cause. Irinotecan should be either discontinued or the doses substantially reduced if Gilbert’s syndrome is suspected. Frequently patients with Gilbert’s syndrome will have an elevation of their bilirubin (especially their indirect bilirubin). Another cause of sensitivity to irinotecan is obstruction of the vessel that delivers bile from the gall bladder to the intestines, called biliary obstruction. As with Gilbert’s syndrome, biliary obstruction leads to a substantial increase in diarrhea and other side effects. Treatment with irinotecan is not recommended if you have this disorder.

How is diarrhea managed?

Diet -  Several modifications to diet will help reduce the discomfort of diarrhea. Food that irritates the GI system should be avoided, such as greasy, spicy, or fried food. You should also avoid milk and milk products because diarrhea may lead to a loss of the enzyme lactase, which breaks down lactose, the sugar found in milk, resulting in temporary lactose intolerance. Because of their high fiber content, vegetables tend to be difficult to digest and should be avoided during episodes of diarrhea. Vegetables, such as cabbage, brussel sprouts, and broccoli, can be particularly problematic.

Your diet should be limited to simple, easy-to-digest food, then expanded as the diarrhea begins to subside. A diet consisting of bananas, rice, applesauce, toast (called the BRAT diet), and clear liquid is a good starting point. Eventually, pasta without sauce, white-meat chicken without skin, scrambled eggs, and other easily digested food can be added, as tolerated.

Fluid intake - Staying hydrated is very important in the management of diarrhea. You must consume enough clear liquids to make up for the volume of fluid lost due to the diarrhea. This amount is in addition to the usual daily intake. You may need to take in 12 to 16 cups or more of fluid per day. In addition to plain water, you should include beverages that contain some sugar and electrolytes, such as broth or Gatorade. Replacement of fluids with plain water alone can lead to low levels of salt or calcium in the blood. These can be life-threatening conditions.

Drug therapy - The first drug to be prescribed for chemotherapy-related diarrhea is usually Imodium^® (loperamide). Loperamide slows the gastrointestinal system and reduces the amount of fluid lost in the stool. Loperamide is effective for managing mild to moderate diarrhea, though it may not work for severe diarrhea. It is an over-the-counter medication that is inexpensive and is available as a pill. If diarrhea continues and is foul-smelling, you may have a toxin in your intestinal tract called Clostridium difficile. If this is the case, you need to contact your doctor because you will need to discontinue the loperamide and begin an antibiotic.

Which chemotherapy drugs cause diarrhea?

Some chemotherapy drugs are more prone to cause diarrhea. Diarrhea is particularly problematic for some drugs that are central to the management of colorectal cancer and cancers of the gastrointestinal tract, including the fluoropyrimidines and irinotecan. Drugs used to treat other cancers may also cause diarrhea, although to a lesser degree.

The cancer treatments that have been reported to cause diarrhea in 30 percent or more of patients are:

• Cosmegen^® (actinomycin)
• Hexalen^® (altretamine)
• Trisenox^® (arsenic trioxide)
• Velcade^® (bortezomib)
• Myleran^®, Busulfex^® (busulfan)
• Xeloda^® (capecitabine)
• Taxotere^® (docetaxel)
• FUDR^® (floxuridine)
• Eulexin^® (flutamide)
• Faslodex^® (fulvestrant)
• Iressa^® (gefitinib)
• Mylotarg^® (gemtuzumab ozogamicin)
• Idamycin^®, Idamycin PFS® (idarubicin)
• Gleevac^®, Glivec^® (imatinib mesylate)
• Proleukin^® (Interleukin-2)
• Camptosar^® (irinotecan)
• DaunoXome^® (liposomal daunorubicin)
• Lysodren^® (mitotane)
• Neumega^® (oprelvekin)
• Taxol^® (paclitaxel)
• Alimta^® (pemetrexed)
• Mithracin^® (plicamycin)
• GM-CSF, Leukine^® (sargramostim)
• Vumon^® (teniposide)

The cancer treatments that have been reported to cause diarrhea in 10 percent to 29 percent of patients are:

• Plenaxis^® (abarelix)
• Paraplatin^® (carboplatin)
• Celebrex^® (celecoxib)
• Cytoxan^®, Neosar^® (cyclophosphamide)
• Aranesp^® (darbepoetin alfa)
• Cerubidine^® (daunorubicin)
• Ontak^® (denileukin diftitox)
• Ellence^® (epirubicin)
• Emcyt^® (estramustine)
• VePesid^®, Toposar^®, Etopophos^® (etoposide)
• Fludara^® (fludarabine)
• Gemzar^® (gemcitabine)
• Hydrea^® (hydroxyurea)
• Zevalin^® (ibritumomab)
• Intron^®, Roferon-A^® (interferon alpha)
• Doxil^® (liposomal doxorubicin)
• Mustargen^® (mechlorethamine)
• Alkeran^® (melphalan)
• Rheumatrex^®, Trexall™ (methotrexate)
• Mutamycin^® (mitomycin)
• Novantrone^® (mitoxantrone)
• Eloxatin^® (oxaliplatin)
• Nipent^® (pentostatin)
• Matulane^® (procarbazine)
• Elitek^® (rasburicase)
• Zanosar^® (streptozocin)
• Thalomid^® (thalidomide)
• Hycamtin^® (topotecan)
• Bexxar^® (tositumomab and iodine 131)
• Velban^® (vinblastine)
• Oncovin^®, Vincasar PFS® (vincristine)
• Navelbine^® (vinorelbine)