Probiotics

Probiotics

PEP Topic 
Chemotherapy-Induced Diarrhea
Description 

Probiotics are live microorganisms that are capable of colonizing the intestinal tract, altering the microflora, and exerting a positive effect on the host. The mechanism by which probiotics exert positive effects remains to be elucidated, but purported mechanisms include

  • Antagonizing pathogens through the production of antimicrobial or antibacterial compounds.
  • Decreasing gut pH by stimulating lactic-acid producing bacteria.
  • Preventing colonization of pathogenic microorganisms by competing for binding sites.
  • Improving immune function.
  • Competing with pathogens for nutrients and growth factors.
  • Producing lactase to aid lactose digestion.
  • Signaling cells to stop production of virulence factors.

Probiotics have been used in the management of diarrhea and constipation. Preoperative probiotics were examined for prevention of infection in patients undergoing colorectal surgery.

Effectiveness Not Established

Research Evidence Summaries

Chitapanarux, I., Chitapanarux, T., Traisathit, P., Kudumpee, S., Tharavichitkul, E., & Lorvidhaya, V. (2010). Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiation Oncology, 5, 31.

doi: 10.1186/1748-717X-5-31
Print

Study Purpose:

To determine if the combination of Lactobacillus acidophilus plus Bifidobacterium bifidum is effective in preventing diarrhea in patients with locally advanced cervical cancer receiving radiation therapy

Intervention Characteristics/Basic Study Process:

Patients were randomized to receive either L. acidophilus plus Bifidobacterium bifidum or placebo capsules. Beginning 7 days before and continuing throughout the entire time of receiving radiotherapy, participants took 2 capsules, 2 times each day before breakfast and dinner. Patients needing antidiarrheal medication were given loperamide (2 mg).

Sample Characteristics:

  • The study reported on 63 patients.
  • The median age was 52 years in the placebo group and 47 years in the study group.
  • The sample was 100% female.
  • All patients had International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IIIB squamous cell carcinoma of the cervix and were scheduled to receive standard treatment for locally advanced cervical cancer (i.e., external beam whole pelvis radiation and brachytherapy plus weekly cisplatin at 40 mg/m2).

Setting:

The study was conducted in Thailand.

Phase of Care and Clinical Applications:

All patients were undergoing the active treatment phase of care.

Study Design:

This was a prospective, randomized, double-blind, placebo-controlled study.

Measurement Instruments/Methods:

The National Cancer Institute Common Toxicity Criteria, version 2, was used.

Results:

  • All patients experienced diarrhea; however, the difference in the severity of the diarrhea was significant (p = 0.002). In the placebo group, 55% of patients experienced grade 1 diarrhea, 42% experienced grade 2, and 3% experienced grade 3. In the study group, 91% experienced grade 1 diarrhea, 9% experienced grade 2, and none experienced grade 3.
  • The intervention group also had a significantly improved stool consistency (p < 0.001).  
  • In the placebo group, 32% of patients needed antidiarrheal medication, compared with only 9% of patients in the study drug group (p = 0.03).

Conclusions:

The prophylactic use of the combination of live L. acidophilus plus Bifidobacterium bifidum was shown to be effective in decreasing the severity of diarrhea.

Limitations:

  • The sample size was small sample with fewer than 100 patients.
  • Cultures were not performed on stool, which could have missed infectious causes of diarrhea. 
  • The use of antimicrobials was not mentioned as exclusion criteria.

Nursing Implications:

The prophylactic use of L. acidophilus plus Bifidobacterium bifidum may decrease the severity of diarrhea, improve stool consistency, and reduce the need for antidiarrheal medication in patients with locally advanced cervical cancer undergoing pelvic radiation with concomitant weekly cisplatin.  Further studies need to be done with larger samples.

Demers, M., Dagnault, A., & Desjardins, J. (2013). A randomized double-blind controlled trial: Impact of probiotics on diarrhea in patients treated with pelvic radiation. Clinical Nutrition (Edinburgh, Scotland), 33(5), 761–767. 

doi: 10.1016/j.clnu.2013.10.015
Print

Study Purpose:

To determine the effectiveness of the probiotic Bifilact® (Lactobacillus acidophilus LAC-361) on moderate and severe treatment-induced diarrhea in patients with pelvic cancer undergoing therapy, with a secondary objective to assess whether Bifilact® decreased or delayed the need for antidiarrheal medication, reduced intestinal pain, decreased hospitalization, lowered the interruption of radiotherapy treatments or doses of both radiotherapy and chemotherapy, and improved the overall well-being of patients during treatment

Intervention Characteristics/Basic Study Process:

Patients were divided into three groups: prostatic cancers, gynecologic cancers without chemotherapy, and gynecologic or rectal cancers with chemotherapy. Then, using double-blind procedures, patients were block-randomized by blocks of two, four, or six patients according to random permutations. A second random block using a higher probiotic dosage was added after an interim analysis. New, random lists were generated for each stratum with a 3:1:1 ratio (higher dose, standard dose, placebo). Nutritional intervention was enacted with a diet teaching to control dietary lipids and providing recommendations on fiber and carbohydrate intake. Yogurt consumption was encouraged.

Sample Characteristics:

  • N = 246  
  • MEAN AGE = Placebo 60.6 years; standard-dose 61.4 years; high-dose 62.0 years
  • MALES: Placebo 63; standard-dose 72; high-dose 66, FEMALES: Placebo 37; standard-dose 28; high-dose 34
  • KEY DISEASE CHARACTERISTICS: Prostate, endometrium, cervix, and rectum
  • OTHER KEY SAMPLE CHARACTERISTICS: Surgery placebo 35%; standard-dose 39%; high-dose 30%; chemotherapy placebo 56%; standard-dose 54%; high-dose 45%

Setting:

  • SITE: Single-site    
  • SETTING TYPE: Outpatient    
  • LOCATION: L’Hôtel-Dieu de Québec University Health Center, Canada

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

Prospective, single-center, placebo-controlled, randomized, double-blinded trial

Measurement Instruments/Methods:

  • World Health Organization (WHO) scale of abdominal pain
  • National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) version 3.0 
  • Fecal incontinence NCI scale version 3.0 stool consistency
  • An adapted Bristol Stool Scale (BSS) was used to facilitate use by patients: grade 1 = normal stools (BSS 1–4); grade 2 = soft stools, in pieces (BSS 5–6), and grade 3 = liquid stools, no shape (BSS 7). 
  • Patients undergoing chemotherapy received a weekly complete blood count. If a patient's neutrophil count was ≤ 1.5 x 109/L, study agent was discontinued.
  • A log book was kept for symptom documentation, stools, and medications such as antidiarrheals. 
  • The European Organization for the Research and Treatment of Cancer's Quality of Life Questionairre C30 (EORTC, QLQ-C30) was completed at baseline, after radiation therapy was completed, and two weeks later.

Results:

229 patients were analyzed. For the primary endpoint among all groups, there was no difference in the effectiveness of the probiotic Bifilact® (Lactobacillus acidophilus LAC-361) on moderate and severe treatment-induced diarrhea. At the 60-day point, there were more patients without moderate and severe diarrhea in the standard-dose group (35%) compared with the placebo group (17%) (hazard ratio of 0.69, p = 0.04). The postsurgical group with patients taking the standard dose had fewer patients without very severe diarrhea compared to the placebo group (97% and 74%, respectively) (p = 0.03). While undergoing therapy, the average number of bowel movements per day during treatment was less than three soft stools (p = 0.80), and the median level of abdominal pain was < 1 based on the NCI scale (p = 0.23).

Conclusions:

Bifilact®, when administered in standard doses to patients with pelvic cancer undergoing therapy, may reduce the risk of radiation-induced grades 2–4 diarrhea towards the end of the treatment. While receiving radiation therapy, a standard dose of probiotics may reduce radiation-induced grade 4 diarrhea in patients who had prior surgery.

Limitations:

  • Key sample group differences that could influence results

Nursing Implications:

Nurses may want to consider offering counseling and education regarding probiotics as a potential alternative approach to reducing radiation-induced diarrhea.

Osterlund, P., Ruotsalainen, T., Korpela, R., Saxelin, M., Ollus, A., Valta, P., … Joensuu, H. (2007). Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: A randomised study. British Journal of Cancer, 97(8), 1028–1034.

doi: 10.1038/sj.bjc.6603990
Print

Study Purpose:

To assess the effect of Lactobacillus and fiber supplementation on tolerability of treatment with chemotherapy containing 5-fluorouracil (5-FU) and to compare the tolerability and frequency of diarrhea with the Mayo regimen (bolus 5-FU) to that of the simplified de Gramont regiment (bolus plus continuous 5-FU)

Intervention Characteristics/Basic Study Process:

Postoperative colorectal cancer (CRC) patients were randomly assigned to receive adjuvant chemotherapy monthly (Mayo regimen) or twice monthly (simplified de Gramont regimen) for 24 weeks. Further randomization determined whether patients received the probiotic Lactobacillus rhamnosus GG gelatin capsules twice daily and daily fiber on cycle days 7–14 for 8 days per month during the 24 weeks of chemotherapy. All patients received dietary counseling and kept nutrition diaries. Treatment-related adverse effects were assessed at every cycle.

Sample Characteristics:

  • The study reported on 148 patients.
  • Median age was 60 years, with a range of 31–75.
  • The sample was 49% female and 51% male.
  • Patients were scheduled to receive adjuvant chemotherapy after surgery for Dukes’ B or C CRC or chemotherapy following surgery for Dukes’ D CRC who were rendered free from metastases by the surgery.

Setting:

The study was conducted at a single-site, outpatient setting in Finland.

Phase of Care and Clinical Applications:

All patients were undergoing the active treatment phase of care.

Study Design:

This was a prospective, randomized trial.

Measurement Instruments/Methods:

The National Cancer Institute of Canada Common Toxicity Criteria, version 2, was used.

Results:

  • Less grade 3-4 diarrhea occurred in patients receiving Lactobacillus supplementation than in those not receiving it (22% versus 37%; p = 0.027). 
  • Less abdominal discomfort (flatulence, borborygmi, or abdominal distention) of any grade occurred in patients receiving Lactobacillus than in those not receiving it (59% versus 75%; p = 0.058). 
  • Only 21% of the patients receiving Lactobacillus had chemotherapy dose reductions due to bowel toxicity as compared to 47% of those who did not receive this supplement (p = 0.0008). 
  • Lactobacillus supplementation had no significant effects on overall treatment toxicity or on the frequency of stomatitis or neutropenia.
  • Fiber supplementation did not affect overall gastrointestinal (GI) toxicity (p = 0.13).

Conclusions:

The frequency of grade 3 or 4 diarrhea and the frequency of abdominal discomfort may be decreased with the use of Lactobacillus rhamnosus supplementation for patients receiving 5-FU-based chemotherapy.

Limitations:

  • Adjuvant chemotherapy for CRC now commonly includes irinotecan, capecitabine, or oxaliplatin.  5-FU was the only adjuvant chemotherapy given in this study.
  • The study was neither placebo-controlled nor blinded to the administration of the fiber or Lactobacillus.
  • Metoclopramide and 5-HT3 inhibitors were used to treat nausea and vomiting. These medications could possibly have effected reported bowel toxicity.
  • No mention was made regarding whether patients were instructed to avoid yogurts and other dairy products produced by fermentation.
  • Use of antimicrobials was not mentioned as an exclusion criterion.

Nursing Implications:

The administration of Lactobacilus rhamnosus GG may decrease the frequency and severity of diarrhea and abdominal discomfort with 5-FU-based chemotherapy. Further placebo-controlled, blinded studies are needed.

Timko, J. (2010). Probiotics as prevention of radiation-induced diarrhoea. Journal of Radiotherapy in Practice, 9(4), 201–208.

doi: 10.1017/S1460396910000087
Print

Study Purpose:

To evaluate the efficacy of probiotics in the prevention of radiation-induced diarrhea

Intervention Characteristics/Basic Study Process:

Patients who had undergone adjuvant, postoperative radiation to the abdominal or pelvic area, alone or in combination with chemotherapy, and were admitted to the hospital were randomized to one of two groups: “5” Strain Dophilus (L group) or Hylak Tropfen Forte drops (H group).

Sample Characteristics:

  • The study reported on 42 patients.
  • The median age of patients in the L group was 62 years with a range of 34–82 years, and the median age of patients in the H group was 67 years with a range of 43–83 years.     
  • The sample was 66% male and 33% female.
  • The majority of patients in the L group had colorectal cancer and the majority of patients in the H group had prostate or rectosigmoid junction cancer.
  • The number of patients in the L group with a body mass index (BMI) of normal weight was equal to the number of patients with an overweight BMI. In the H group, more patients had an overweight BMI than a normal BMI.
  • In the L group, 55% of patients also received chemotherapy. In the H group, 50% of patients also received chemotherapy.
     

Setting:

This study was conducted at a single-site, inpatient setting in Ruzomberok, Slovakia.

Phase of Care and Clinical Applications:

All patients were undergoing the active treatment phase of care.

Study Design:

This was a randomized, parallel-group, nonplacebo controlled trial.

Measurement Instruments/Methods:

Patient diaries were used to record the number and consistency of stools, presence of bleeding or abdominal pain, and use of antidiarrheals or antibiotics.

Results:

  • Patients in the L group had a higher number of daily bowel movements (BMs) (n = 4.16, range = 1.2–9.7) than in the H group (n = 2.52, range = 0.7–5.3).
  • In the second week, the weekly number of BMs was significantly higher in the L group (p < 0.01) compared to the H group.
  • The number of BMs in the H group increased at week 3.
  • A significant increase was reported in the number of BMs in patients receiving only radiation versus radiation plus chemotherapy.
  • Fewer patients in the L group (27%) required an antidiarrheal (specifically diphenoxylate) compared to the H group (55%).
  • Fewer patients in the L group (9%) required antibiotics versus in the H group (25%).
  • Abdominal pain was similar between groups with 25% of patients reporting the side effect in the L group compared to 22% in the H group.
  • One subject in the H group reported blood in the stool at day 9.

Conclusions:

Probiotics  may be effective in the prevention of radiation-induced diarrhea.

Limitations:

  • The sample size was small, with fewer than 100 patients.
  • A control group was not included.
  • Patients' diets and the radiation technique could have varied between groups.

Nursing Implications:

The use of probiotics may have some benefit in the prevention of radiation-induced diarrhea; however, more studies (including control arms) are needed.

Systematic Review/Meta-Analysis

Salari, P., Nikfar, S., & Abdollahi, M. (2012). A meta-analysis and systematic review on the effect of probiotics in acute diarrhea. Inflammation & Allergy Drug Targets, 11(1), 3–14.

Print

Purpose:

To clarify the efficacy of probiotics in children and adults

Search Strategy:

  • Databases searched were PubMed, Web of Science, Scopus, and the Cochrane Database.
  • Search keywords were probiotics and diarrhea.
  • Studies were included in the review if they were randomized clinical trials (RCTs) and involved children.
  • Studies were excluded if they were uncontrolled trials or the results did not address study goals.

Literature Evaluated:

  • A total of 1,228 references were retrieved.
  • The Jadad scale quality rating was used to evaluate the literature.

Sample Characteristics:

  • The final review involved 20 studies with total sample of 3,867 patients. Sample sizes ranged from 69–913 patients.
  • Most trials involved children. Two studies were included regarding radiation-induced diarrhea and one trial involved chemotherapy-related diarrhea. These studies were not included in the meta-analysis.

Results:

The effect size for probiotics compared to placebo in 19 trials related to duration of diarrhea was -0.67 (95% confidence interval [CI] = -0.95–0.38) in favor of probiotics. Heterogeneity was statistically significant. Findings included evaluation of duration of diarrhea, hours of fever, duration of hospitalization, duration of vomiting, and number of stools per day. Authors reviewed subsets of information for children, adults, cases of amebiasis and clostridium difficile, HIV, and radiation or chemotherapy.

Conclusions:

Taken as a whole, authors concluded insufficient evidence exists for the efficacy of probiotics for different types of diarrhea in children or adults.

Limitations:

  • Very few of the trials were relevant to oncology.
  • Trials involved both children and adults. However, only the trials involving children were included in the meta-analysis. 
  • High heterogeneity existed among the studies. 
  • Variations in specific probiotics may have influenced results.
  • The authors noted the need for agreement among researchers in defining measurements including what constitutes the end of diarrhea.

Nursing Implications:

These findings did not provide strong support for the use of probiotics for prevention or management of diarrhea in patients receiving radiation or chemotherapy. Overall evidence in all groups was limited by a number of factors. The specific type, dosages, and timing of probiotic use varied.


Menu