Usually when we discuss the side effects of chemotherapy with patients we bring up the problems of nausea/vomiting and diarrhea. When I became a fellow, the platinum-containing chemotherapy drugs had just become standard drugs for the treatment of various cancers—these were very powerful inducers of emesis and, as a consequence, much effort over the next 15 years was placed on the development of effective antiemetics. To a large degree these efforts have been successful.
Not as much attention has been devoted, however, to diarrhea. This is despite the fact that it is probably an even more common and distressing problem for cancer chemotherapy patients. One study estimated that as many as 80% of patients who were undergoing chemotherapy experienced diarrhea, and one-third experienced severe diarrhea. So this is not a minor problem. The rapid turnover rate of the mucosa of the gastrointestinal tract makes it particularly susceptible to the toxicity of chemotherapy drugs, similar to the bone marrow. The exigency and urgency of frequent, sudden bowel movements that is often characteristic of chemotherapy-related diarrhea can make car travel a misery. Patients complain of soiled garments and a need to carry changes of clothing.
Various drugs can be responsible. Most noteworthy are the fluoropyrimidines, like 5-fluorouracil and capecitabine (Xeloda), and irinotecan. 5FU and irinotecan both can damage the intestinal mucosa, leading to a loss of epithelium in the luminal GI tract with increased secretion of fluid by the small bowel in compensation—this overwhelms the capacity of the colon to re-absorb the fluid. There are also several other mechanisms by which the various drugs utilized in cancer treatment can induce diarrhea.
This past week, I had a longstanding 73-year-old patient who has suffered from advanced colon cancer for several years and who had survived and progressed on two prior chemotherapy regimens. She started the standard third chemotherapy regimen, an oral drug which is on a four-week cycle but, because it can cause significant side effects, I usually have the patients come to clinic after two weeks in the first cycle in order to monitor for side effects; the nadir for side effects is mid-cycle. Sure enough, the patient came to clinic with a complaint of four days of significant diarrhea, with 10-12 bowel movements daily that were uncontrolled by the aggressive use of loperamide (10-12 tablets daily). Her urine output was decreased, which suggested dehydration, and blood tests in clinic showed a creatinine of 2.7 (normal up to 1.0) confirming severe dehydration. I sent her to the emergency room for admission. With aggressive fluids and aggressive loperamide use, her creatinine returned to normal after 36 hours and her diarrhea resolved after 48 hours and she was discharged to home.
For the next cycle of her chemotherapy drug, we will prescribe a reduced dose of the drug. Interestingly, her serum CEA (carcinoembryonic antigen), a marker of the extent of her colon cancer, had come down by 30%, a not-uncommon phenomenon when patients have severe side effects from their chemotherapy. Whatever metabolic phenomenon led to her intolerability of the drug suggests that she, in effect, had a higher physiologic level of the drug than intended, leading to the severe side effect. Simultaneously her tumor was exposed to a higher level of the chemotherapy drug than intended and thus had a better response than might have otherwise occurred.
Loperamide, also known as Imodium, is the most commonly used drug for chemotherapy-related diarrhea. It acts like morphine, slowing the passage of intestinal contents through the large bowel. Because of this, there is an opportunity for more liquid to be absorbed from the fecal material. Interestingly it was first synthesized by Paul Janssen of Janssen Pharmaceuticals. It was FDA-approved in 1976. It does have some side effects but is generally well tolerated. Most diarrhea will be controlled by the aggressive use of loperamide.
For diarrhea refractory to loperamide, the next drug that I tend to try is octreotide. This requires parenteral administration so the patient usually needs to be in the hospital for this.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
