Results from a phase II/III study conducted in India* shows that a high concentration of multi-strain probiotic helps to reduce mild to moderate episodes of chemotherapy-induced diarrhea (CID) in cancer patients. [1]

The randomized, double-blind, placebo-controlled single center study enroled 291 patients.

The final results of the study, presented at 2018 annual meeting of the European Society for Medical Oncology – ESMO 2018 by lead investigator Atul Sharma, Professor of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India, confirm that the although the study did not meet its primary endpoint, probiotics did helped reduce chemotherapy-induced diarrhea or CID.

?This is probably the first large, randomized, placebo-controlled study to look at the role of multi-strain, high dose probiotic in chemotherapy-induced diarrhea,? Sharma said.

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?Though [the study] did not meet its primary endpoint in reducing incidence of grade 3 and 4 diarrhea [statistical significance was not met], it helped to reduce the incidence of all grades of diarrhea. The probiotic also helped in reducing levels of inflammatory markers, the significance of which needs to be ascertained,? he noted.

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Study results
The incidence of grade 3 diarrhea episodes was 8.0% for patients on probiotics, and 4.1% for those on placebo (p=0.088); and for grade 4 episodes the respective incidences were 2.0% and 0% (p=0.050). For all grades of diarrhea, there were 199 and 220 episodes in probiotic and placebo groups respectively (p=0.019).

Analysis of serum vascular endothelial growth factor (VEGF), clusterin, and fecal calprotectin showed levels were reduced in patients taking the multi-strain probiotic.

Chemotherapy changes the consistency of the gut microflora and as such it can lead to some serious side-effects.

Under-reported
“Chemotherapy-induced diarrhea is an under-reported, unpleasant, and sometimes a serious side-effect of chemotherapy. It may be associated with weight-loss, malnutrition, fatigue and malaise, electrolyte imbalance and inability to deliver full dose of chemotherapy on time. It may also cause loss of body fluid resulting into acute renal injury and rarely death,? Sharma explained.

To determine whether it improved the balance of intestinal flora and as such reduce these side effects, the study investigated the efficacy of a high potency multi-strain probiotic on patients experiencing CID while receiving fluropyrimidines and/or irinotecan-based cancer therapy.

The multi-strain probiotic consisted of 900 billion colony forming units (CFU) sachet of four strains of lactobacillus, three strains of bifidobacteria and one strain of streptococcus thermophiles. Patients were randomized to receive either one sachet of probiotic twice daily (n=145) or one sachet of placebo twice daily (n=146), started 14 days prior to chemotherapy, and continued for two weeks following chemotherapy cycle three. The vast majority of patients were men, approximately 80%; and aged approximately 46 years. There were no increased incidence of infections.

Simple approach
“These data suggest that probiotics have potential to be a simple and novel approach in the reduction of chemotherapy-induced diarrhea, however confirmatory studies are awaited. As probiotics are living microorganisms there is potential risk of iatrogenic infection in immune-compromised cancer patients, therefore safety data and adverse events associated with probiotic administration could influence their future role in prevention of chemotherapy induced diarrhea,? said Michal Mego, MD, PhD, Head of 2nd Department of Oncology, Comenius University, National Cancer Institute, Bratislava, Slovak Republic, commenting on the study results.

“Due to the effect of the gut microbiome on response and toxicity in cancer patients treated with immune checkpoint inhibitors and the recently initiated trials with fecal transplantation to improve outcome of checkpoint inhibitors, this study is of interest,? added John B.A.G. Haanen, MD, PhD, Chief Scientific Officer Immunotherapy, Netherlands Cancer Institute, Amsterdam and Professor of Translational Immunotherapy of Cancer, Leiden University Medical Center, Leiden, The Netherlands, reflecting on the accumulation of evidence for the effect of the gut microbiome on cancer therapy.

?It’s currently unknown? whether probiotics used in this RCT positively or negatively influence the immune system, and with more patients being treated with immunotherapy, before embarking on large-scale usage of probiotics to reduce chemotherapy-induced diarrhoea, their effect on the immune system should be investigated,? Haanen concluded.

The final results of a phase II/III, randomized, double blind, placebo-controlled study (Abstract 1682O_PR)? to investigate the efficacy of a high potency multistrain probiotic, on chemotherapy induced diarrhea in cancer patients receiving Fluropyrimidines and/or Irinotecan based therapy, will be presented by lead investigator Atul Sharma, Professor of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India during Proffered paper Session on Sunday, 21 October 2018 14:45 to 16:15 (CEST) in Room 20 – Hall B3.

References
[1] Sharma A, Chaudhary S.P., Raina V.m Shukla N.K., Sreenivas V., Prakash S., Priyatma P., Bharti S. Final results of a phase II/III, randomized, double blind, placebo-controlled study to investigate the efficacy of a high potency multistrain probiotic, on chemotherapy induced diarrhea in cancer patients receiving fluropyrimidines and/or irinotecan based therapy. Abstract 1682O_PR. Annals of Oncology, Volume 29 Supplement 8 October 2018.

* Clinical Trial Registry India Identifier : CTRI/2009/091/001042


Last Editorial Review: October 21, 2018

Featured Image: ESOM 2018. Courtesy: ? 2018 European Society for Medical Oncology. Used with permission.

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