MANAGEMENT OF

CHEMOTHERAPY- INDUCED
DIARRHEA WITH PROBIOTICS
Hayley Billingsley

Outline
Etiology and Pathophysiology
Incidence and Prevalence
Grading Criteria
Medical Management and Treatment
MNT Management and Treatment- RDs Role
Probiotic Studies
Risks

Etiology of CID
Chemotherapy Induced Diarrhea = CID
Chemotherapy

May

be curative or meant to prolong life or reduce

symptoms

Traditional chemotherapeutic agents are cytotoxic

Work

by killing cells that rapidly divide

Pathophysiology OF CID

Gastrointestinal toxicity of chemotheraputic agents

Complications that arise include diarrhea, constipation, colitis

and intestinal perforation

Most commonly seen with fluoropyrimidines

(fluorouracil and capecitabine) and irinotecan

Incidence and Prevalence

1,685,210 Americans are expected to be diagnosed with

cancer in 2016

In the US in 2012, 582,607 peopleabout 1,596 people a day

died of cancer

2nd most common cause of death in America

Incidence and Prevalence

650,000 patients are treated with outpatient chemotherapy

alone each year
CID can occur in up to 80% of patients depending on the
chemotherapy administered
CID can be dose limiting:
Dosing

delays (71% of patients)

Dosing reductions (45% of patients )

This can easily impact survival

Secretory Diarrhea with an Exudative

component

+Mucus, proteins, and red and white blood cells from lymphatic system and
blood vessels in the GI tract

NCI Common Terminology Criteria For Adverse Events

(CTCAE) version 4.0

Diarrhea
Definition:

A disorder characterized by frequent and

watery bowel movements.

Grade

Criteria

Increase of <4 stools per day over baseline; mild increase in ostomy
output compared to baseline

Increase of 4 - 6 stools per day over baseline; moderate increase in

ostomy output compared to baseline

Increase of >=7 stools per day over baseline; incontinence;

hospitalization indicated; severe increase in ostomy output compared to
baseline; limiting self care ADL

Life-threatening consequences; urgent intervention indicated

Death

Impact Of CID

CID can cause

Fluid depletion(dehydration, AKI)
Electrolyte abnormalities (hypokalemia, metabolic acidosis
hyponatremia, hypernatremia)
Malnutrition (malabsorption)
Hospitalization
Treatment Delay
Increased cost of care
Reduced quality of life
Diminished compliance

Medical Management

Loperamide (Imodium)
1st

Octreotide Acetate

line medication

somatostatin analog that acts on epithelial cells

long-acting repeatable (LAR) octreotide

MNT For CID- The RDs Role

Small, frequent meals

Consider MVI
Monitor weight and intake
Soluble fiber
oatmeal,

barley, applesauce, potatoes, bananas.

Calorie containing, low-osmolality beverages

Gatorade
Pedialyte

Protein- rich foods

BRAT Diet

MNT For CID

Avoid:
Alcohol and caffeine
Spicy and high fat foods
High-sorbitol juices

High insoluble fiber foods

n
n
n

prune and apple juices

raw fruits and vegetables
whole grains, popcorn
nuts and legumes

Sugar-free products containing sugar alcohols

malitol, xylitol, soribitol, mannitol

Probiotics for CID

Change composition of intestinal microflora

Form

a physical protective barrier

Possibly bind and degrade carcinogens

Anti-inflammatory effects on mucosa
Produce acidic environment through secretion of
lactic acid

Studies
1.

2.

Lactobacillus supplementation for diarrhoea

related to chemotherapy of colorectal cancer: A
randomized study
Prevention of irinotecan induced diarrhea by
probiotics: A randomized double blind, placebo
controlled pilot study.

(1) Lactobacillus Supplementation

Purpose:

Evaluating the efficacy of Lactobacillus rhamnosus GG (and guar

gum) supplementation in reducing 5- Fluoroacil (5-FU)- based
chemotherapy toxicity.

Subjects
150 subjects, 18-75 YO, deemed appropriate for chemotherapy
Histologically confirmed Dukes B or C or Metastatic Colorectal
Cancer

Design
open-label, prospective, phase III
Lactobacillus
randomized
N=97
single institution
Lactobacillus and
Guar Gum
2x3 factorial design

Control
N=51

De
Gramont

Mayo

N=48

N=49

(N= 25)

(N=25)

N=25

N=26

(1) Lactobacillus Supplementation

Methods
lactobacillus

caplets

n administered

12 1010 per day

Medical

history, physical exam, blood cell counts, serum

chemistry
Adverse effects assessed and graded using the CTCAE.
Evaluations occurred
n 21

days pre-treatment
n weekly during treatment
n 2-6 months post-treatment.
Results

analyzed

n P-value

<0.05 was considered significant

(1) Lactobacillus Supplementation

Results
Frequency

of grade 3-4 diarrhea was lower among

patients who received Lactobacillus (22 vs. 37%,
P=0.027)
n Abdominal

discomfort was less (P= 0.025).

n Less patients required hospital care for bowel toxicity
(P=0.021)
n Less required dose-reductions due to bowel toxicity
(0.0008).

Differences were not observed with guar gum

supplementation.

(1) Lactobacillus Supplementation

(1) Lactobacillus Supplementation

Strengths
Dose and type of probiotic supplement recorded
Compliance monitored
Large sample size
Different regimens of chemotherapy administration

Limitations
Not placebo controlled OR blinded
Did not investigate other chemotherapy drugs known to commonly
cause diarrhea or Leucovorin (often used in combination with 5FU and diarrhea risk)

(1) Lactobacillus Supplementation

Daily lactobacillus supplementation may be a
beneficial, cost-effective aid in management of 5FU related diarrhea
Further study is warranted.

(2) Prevention of Irinotecan-induced diarrhea

Purpose

Subjects

To determine the effectiveness of probiotic formula Colon

Dophilus in prevention of Irinotecan-induced diarrhea in
metastatic colon cancer patients
49 total patients, over 18 years of age with histologically proven
colorectal cancer

Design
Multicenter
Randomized
Placebo controlled
Double-blinded
N= 23 placebo group, N=23 probiotic group

(2)Prevention of irinotecan-induced diarrhea

Methods
Drug

administration : Colon Dophilus

n administered

at a dose of x 1 caplets per day orally for 12

weeks
Supportive

care recorded by patients

Adverse effects assessed and graded using the CTCAE.
Results analyzed
n P-value

<0.05 was considered significant

(2)Prevention of irinotecan-induced
diarrhea

Results
Probiotic

group vs placebo did lead to a reduction in

incidence of severe diarrhea (grade 3-4) 0% vs 17.4%,
(p=0.11)
Probiotic group vs placebo also had a reduction in overall
incidence of diarrhea, 39.1% vs 60.9% (p= 0.24)
Probiotic group also used less loperamide, reported less
bloating from examination of study diaries (82.6% were
turned in)

(2)Prevention of irinotecan-induced diarrhea

(2)Prevention of irinotecan-induced diarrhea

Strengths
Dose

and type of probiotic supplement recorded

Strong design
Different schedules of irinotecan

Limitations
Compliance

to study probiotic not recorded

Small sample size due to premature termination

(2)Prevention of irinotecan-induced
diarrhea

Conclusion: Probiotic administration is safe and

may lead to a reduction in the incidence and
severity of diarrhea and gut toxicity due to
chemotherapy. More study is warranted.

Risks: GRAS

What does this mean for the oncology patient

with heightened risk of infection?
Afflicted integrity of epithelium lining digestive tract (mucositis) +
neutropenia
Both studies noted that not a single patient received an infection
Adverse effects, including sepsis with probiotic strain found in
blood culture, are in the literature, also noted as being rare
Further study is warranted

Questions?

Citations
1.

2.

Stein, A., Voigt, W., & Jordan, K. (2009). Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management. Therapeutic
advances in medical oncology.
US Cancer Statistics Working Group. (2013). United States cancer statistics: 19992010 incidence and mortality web-based report. Atlanta: US
Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute.

3.

Richardson, G., & Dobish, R. (2007). Chemotherapy induced diarrhea. Journal of Oncology Pharmacy Practice, 13(4), 181-198.

4.

Arnold RJG, Gabrail N, Raut M, Kim R, Sung JCY, Zhou Y. Clinical implications of chemotherapy-induced diarrhea. J Support Oncol 2005; 3: 22732.

5.

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Muehlbauer, P. M., Arlene Davis, R. N., Rachael Drabot, M. P. H., CNSD, R., Rawlings, B. L., & Elizabeth Kiker, R. N. (2009). Putting evidence into practice:
evidence-based interventions to prevent, manage, and treat chemotherapy-and radiotherapy-induced diarrhea. Clinical journal of oncology nursing,
13(3), 336.
Stern, J. M. (2002). Management of Chemotherapy-Induced Diarrhea: Nutritional Support and Diet Alterations. Retrieved March 06, 2016, from http://
www.cmecorner.com/macmcm/ons/ons2002_05.htm
Gibson, R. J., & Keefe, D. M. (2006). Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and prevention strategies.
Supportive Care in Cancer, 14(9), 890-900.
Redman, M. G., Ward, E. J., & Phillips, R. S. (2014). The efficacy and safety of probiotics in people with cancer: a systematic review. Annals of
Oncology, mdu106.
Miller, A. C., & Elamin, E. M. (2009). Use of probiotics for treatment of chemotherapy-induced diarrhea: is it a myth?. Journal of Parenteral and Enteral
Nutrition, 33(5), 573-574.
sterlund, P., Ruotsalainen, T., Korpela, R., Saxelin, M., Ollus, A., Valta, P., ... & Joensuu, H. (2007). Lactobacillus supplementation for diarrhoea related
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Mego, M., Chovanec, J., Vochyanova-Andrezalova, I., Konkolovsky, P., Mikulova, M., Reckova, M., ... & Lagin, A. (2015). Prevention of irinotecan induced
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