BACKGROUND: Treament-related diarrhoea is one of the most common and troublesome adverse effects related to chemotherapy or radiotherapy in people with cancer. Its reported incidence has been as high as 50% to 80%. Severe treatment-related diarrhoea can lead to fluid and electrolyte losses and nutritional deficiencies and could adversely affect quality of life (QoL). It is also associated with increased risk of infection in people with neutropenia due to anticancer therapy and often leads to treatment delays, dose reductions, or treatment discontinuation. Probiotics may be effective in preventing or treating chemotherapy- or radiotherapy-induced diarrhoea.
OBJECTIVES: To evaluate the clinical effectiveness and side effects of probiotics used alone or combined with other agents for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 7), MEDLINE (1946 to July week 2, 2017), and Embase (1980 to 2017, week 30). We also searched prospective clinical trial registers and the reference lists of included studies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating the effects of probiotics for prevention or treatment of chemotherapy- or radiotherapy-related diarrhoea in people with cancer.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses. If meta-analysis was not possible, we summarised the results narratively.
MAIN RESULTS: We included 12 studies involving 1554 participants. Eleven studies were prevention studies, of which seven compared probiotics with placebo (887 participants), one compared two doses of probiotics with each other and with placebo (246 participants), and three compared probiotics with another active agent (216 participants).The remaining study assessed the effectiveness of probiotics compared with placebo for treatment of radiotherapy-related diarrhoea (205 participants).For prevention of radiotherapy (with or without chemotherapy)-induced diarrhoea, review authors identified five heterogeneous placebo-controlled studies (with 926 participants analysed). Owing to heterogeneity, we could not carry out a meta-analysis, except for two outcomes. For occurrence of any diarrhoea, risk ratios (RRs) ranged from 0.35 (95% confidence interval (CI) 0.26 to 0.47) to 1.0 (95% CI 0.94 to 1.06) (three studies; low-certainty evidence). A beneficial effect of probiotics on quality of life could neither be demonstrated nor refuted (two studies; low-certainty evidence). For occurrence of grade 2 or higher diarrhoea, the pooled RR was 0.75 (95% CI 0.55 to 1.03; four studies; 420 participants; low-certainty evidence), and for grade 3 or higher diarrhoea, RRs ranged from 0.11 (95% CI 0.06 to 0.23) to 1.24 (95% CI 0.74 to 2.08) (three studies; low-certainty evidence). For probiotic users, time to rescue medication was 36 hours longer in one study (95% CI 34.7 to 37.3), but another study reported no difference (moderate-certainty evidence). For the need for rescue medication, the pooled RR was 0.50 (95% CI 0.15 to 1.66; three studies; 194 participants; very low-certainty evidence). No study reported major differences between groups with respect to adverse effects. Although not mentioned explicitly, no studies reported deaths, except one in which one participant in the probiotics group died of myocardial infarction after three sessions of radiotherapy.Three placebo-controlled studies, with 128 analysed participants, addressed prevention of chemotherapy-induced diarrhoea. For occurrence of any diarrhoea, the pooled RR was 0.59 (95% CI 0.36 to 0.96; two studies; 106 participants; low-certainty evidence). For all other outcomes, a beneficial effect of probiotics could be neither demonstrated nor refuted (one to two studies; 46 to 106 participants; all low-certainty evidence). Studies did not address quality of life nor time to rescue medication.Three studies compared probiotics with another intervention in 213 participants treated with radiotherapy (with or without chemotherapy). One very small study (21 participants) reported less diarrhoea six weeks after treatment when dietary counselling was provided (RR 0.30, 95% CI 0.11 to 0.81; very low-certainty evidence). In another study (148 participants), grade 3 or 4 diarrhoea occurred less often in the probiotics group than in the control group (guar gum containing nutritional supplement) (odds ratio (OR) 0.38, 95% CI 0.16 to 0.89; low-certainty evidence), and two studies (63 participants) found less need for rescue medication of probiotics versus another active treatment (RR 0.44, 95% CI 0.22 to 0.86; very low-certainty evidence). Studies did not address quality of life nor time to rescue medication.One placebo-controlled study with 205 participants addressed treatment for radiotherapy-induced diarrhoea and could not demonstrate or refute a beneficial effect of probiotics on average diarrhoea grade, time to rescue medication for diarrhoea (13 hours longer in the probiotics group; 95% CI -0.9 to 26.9 hours), or need for rescue medication (RR 0.74, 95% CI 0.53 to 1.03; moderate-certainty evidence). This study did not address quality of life.No studies reported serious adverse events or diarrhoea-related deaths.
AUTHORS' CONCLUSIONS: This review presents limited low- or very low-certainty evidence supporting the effects of probiotics for prevention and treatment of diarrhoea related to radiotherapy (with or without chemotherapy) or chemotherapy alone, need for rescue medication, or occurrence of adverse events. All studies were underpowered and heterogeneous. Severe side effects were absent from all studies.Robust evidence on this topic must be provided by future methodologically well-designed trials.
Post chemotherapy and radiotherapy diarrhoea is a troublesome complication. This study highlights the level of evidence of the use of probiotics in these patients. It is useful in clinical practice.
These results are what I would have expected. However, this article does not provide clear evidence.
Many patients take probiotics, usually because of newspaper articles advocating probiotics for "bowel health", but sometimes to try to reduce diarrhea from radiation therapy. It is useful to have this review to counter anecdotal reports. As so often is the case, it is depressing to see so much work is put into studies, subsequently considered to have low scientific merit.
Probiotics are not routinely recommended by Oncologists for treatment related complications such as diarrhoea. This meta-analysis agrees that the data is insufficient; their conclusion that probiotics appear harmless should be taken with caution, especially in view of emerging data that "probiotics perturb rather than aid in microbiota recovery back to baseline after antibiotic treatment in humans" (Cell, 06 Sep 2018)
The review is not very useful: it suggests a positive effect but the level of evidence is very low. It practically rules out side effects.
Insufficient evidence, but probiotics may be safe.
As stated by the authors, further robust data are needed. The problem is of utmost importance for cancer patients and clinicians. Well designed RCTs, not commercially driven, are eagerly needed.
The inclination to prescribe probiotics for chemo/radiotherapy related diarrhoea is based on a belief of utility and 'can not possibly harm' assumption and a placebo effect of prescribing a 'medicine' to mitigate the symptoms of diarrhoea. The article clarifies the evidence available and is therefore of use.