Diarrhea In Cancer Patients Research Articles

Effect of probiotic supplementation on chemotherapy- and radiotherapy-related diarrhoea in patients with cancer: an umbrella review of systematic reviews and meta-analyses.

To date, several systematic reviews and meta-analyses (SRMA) have investigated the effects of probiotics, but the certainty of the evidence for an effect on chemotherapy and radiotherapy-related diarrhoea has not been assessed. We conducted an overview of SRMA, searching MEDLINE, Scopus, and ISI Web of Science from inception up to February 2022. We summarised the findings of eligible SRMA. Subsequently, we included randomised clinical trials (RCT) from the SRMA in meta-analyses, using a quality effects model to calculate the OR and 95 % CI for each outcome. We used ‘A Measurement Tool to Assess Systematic Reviews’ and the Cochrane risk of bias tool to assess the methodological quality of the SRMA and their RCT, respectively. We used the ‘Grading of Recommendations Assessment, Development, and Evaluation’.We included thirteen SRMA, which reported pooled effect sizes for chemotherapy and radiotherapy-related diarrhoea based on a total of eighteen RCT. Our meta-analyses demonstrated statistically significant beneficial effects from probiotics on all outcomes, except stool consistency; diarrhoea (any grade) OR 0·35 (95 % CI 0·22, 0·54), grade ≥ 2 diarrhoea 0·43 (0·25, 0·74), grade ≥ 3 diarrhoea 0·30 (0·15, 0·59), use of medication 0·49 (0·27, 0·88), soft stool 1·10 (0·44, 2·76) and watery stool 0·52 (0·29, 1·29). Probiotics use can reduce the incidence of diarrhoea in cancer patients in chemotherapy and radiotherapy, but the certainty of evidence for significant outcomes was very low and low.

Review on Dietary Factors in Fermented Foods and their Efficacy in Disease Management

Abstract: The process of preservation of various food sources, over time, gave rise to fermented foods. Traditionally, each ethnic group has its distinct fermented food(s) incorporated into their diet, both as culinary enjoyment and nutrition. Fermentation increases nutrient availability and enhances the texture and flavor of the original food. The benefits of fermented food consumption and potential probiotic intake are discussed in this review. The review describes mechanism(s) of action of bioactive components from fermented foods on the human system, their role in health management, and an overview of the role of fermented foods in improving diseases, namely obesity, cardiovascular diseases (CVDs), inflammatory bowel disease (IBD), hematological cancers, and radiation-induced diarrhea in cancer patients and allergies are briefly reviewed.

Could paraprobiotics be a safer alternative to probiotics for managing cancer chemotherapy-induced gastrointestinal toxicities?

Clinical oncology has shown outstanding progress improving patient survival due to the incorporation of new drugs. However, treatment success may be reduced by the emergency of dose-limiting side effects, such as intestinal mucositis and diarrhea. Mucositis and diarrhea management is symptomatic, and there is no preventive therapy. Bacterial and fungal-based compounds have been suggested as an alternative for preventing the development of diarrhea in cancer patients. Using probiotics is safe and effective in immunocompetent individuals, but concerns remain during immunosuppressive conditions. Paraprobiotics, formulations composed of non-viable microorganisms, have been proposed to overcome such limitation. The present literature review discusses current evidence regarding the possible use of paraprobiotics as an alternative to probiotics to prevent gastrointestinal toxicity of cancer chemotherapy.

Orally Administered Probiotics in the Prevention of Chemotherapy (± Radiotherapy)-Induced Gastrointestinal Toxicity: A Systematic Review With Meta-Analysis of Randomized Trials.

Chemoradiotherapy-induced gastrointestinal toxicity may lead to a significant impairment of the oncological patient's quality of life, as well as to reduced adherence to the treatment, which may have a negative impact on survival and mortality rates. The aim of this review was to investigate whether oral probiotic administration prevents chemotherapy (± radiotherapy)-induced gastrointestinal toxicity, particularly diarrhea. We searched the MEDLINE, Web of Science, and SCOPUS databases for randomized controlled trials in English published between 1990 and 2020. We conducted statistical data analyses expressing the treatment effect size as a risk ratio (RR) together with a 95% confidence interval (CI). Implications are based on trials rated as having a low risk of bias (RoB). We included 8 trials (n = 697 participants), from which 3 studies rated as low RoB contained primary endpoint data; the risk of developing grade 3/4 diarrhea in patients receiving probiotics was reduced by 78% compared to the control group (RR = 0.22 [95% CI 0.05-1.08]; P = .06; n = 114 participants). Probiotics showed preventive effects in patients treated with chemotherapy alone (RR = 0.34 [0.12-0.94]; P = .04, n = 121 participants) and in patients with colorectal cancer (RR = 0.56 [0.34-0.92]; P = .02; n = 208 participants). The reduction in the incidence of overall diarrhea was not significant. Probiotics failed to prove a preventive effect of statistical significance against the development of severe and overall diarrhea in cancer patients treated with chemotherapy (± radiotherapy). However, we cannot rule out that the effects of probiotics are clinically relevant, especially in certain subgroups of patients. This needs to be clarified in further well-performed studies.

Norovirus in Cancer Patients: A Review.

Norovirus (NoV) is the leading cause of viral-related diarrhea in cancer patients, in whom it can be chronic, contributing to decreased quality of life, interruption of cancer care, malnutrition, and altered mucosal barrier function. Immunosuppressed cancer patients shed NoV for longer periods of time than immunocompetent hosts, favoring quasispecies development and emergence of novel NoV variants. While nucleic acid amplification tests (NAATs) for NoV diagnosis have revolutionized our understanding of NoV burden of disease, not all NAATs provide information on viral load or infecting genotype. There is currently no effective antiviral or vaccine for chronic NoV infections. Screening for inhibitors of NoV replication in intestinal organoid culture models and creation of NoV-specific adoptive T cells are promising new strategies to develop treatments for chronic NoV in immunosuppressed patients. Herein we summarize data on the epidemiology, clinical manifestations, diagnostic challenges, and treatment of NoV infection in patients with cancer.

Assessment of diarrhea as side effect of oral targeted antineoplastic agents in clinical practice.

Diarrhea is one of the most frequent class adverse events associated with targeted oral antineoplastic agents (OAAs). Our objective was to analyze the incidence, characteristics, and severity of diarrhea in cancer patients in clinical practice. An observational, longitudinal, and prospective study of cancer outpatients treated with targeted OAAs was carried out in a tertiary hospital. Targed OAAs analyzed were anaplastic lymphoma kinase inhibitors, BCR-ABL inhibitors, cyclin-dependent kinase inhibitors, epidermal growth factor receptor inhibitors, mTOR inhibitors, poly (ADP-ribose) polymerase inhibitors, and vascular endothelial growth factor receptor inhibitors. Patients were given a data collection form to record daily the number, severity (CTCAE version 5.0), and characteristics of stools during the first 30days of treatment with OAAs. Multivariate analysis was performed to identify risk factors associated with the incidence of diarrhea. We analyzed 240 patients, of whom 28.7% experienced diarrhea (25.4% grades 1-2 and 3.3% grades 3-4). Patients treated with EGFR and VEGFR inhibitors had a higher incidence of diarrhea. The multivariate analysis revealed that taking the OAA with food was associated with a lower risk of diarrhea (OR = 0.404 [0.205-0.956], p = 0.038). More than a third of patients in treatment with OAAs presented diarrhea (any grade), and 22.1% of stools were semi-liquid/liquid. In multivariate analysis, taking the OAA on an empty stomach was associated with a statistically significant increase in the incidence of diarrhea.

Lactobacillus Kefiri LKF01 (Kefibios®) for Prevention of Diarrhoea in Cancer Patients Treated with Chemotherapy: A Prospective Study.

Diarrhoea is one of the main side effects that cancer patients face. The literature showsthat the incidence of chemotherapy (CT)-induced diarrhoea (grade 3–4) in treated patients is in the range of 10–20%, particularly after 5-fluorouracil (5-FU) bolus or some combination therapies of irinotecan and fluoropyrimidines. The aim of the present study was to evaluate the clinical effectiveness of Lactobacillus kefiri LKF01 (Kefibios®) in the prevention or treatment of CT-related diarrhoea in the cancer population. We conducted a prospective observational study. Patients enrolled were adults treated for at least four months with 5-FU-based CT. Kefibios® was administered to patients every day. The primary outcome was the evaluation of the incidence of grade 3–4 CT-induced diarrhoea. We included 76 patients in the final analysis. A 6.6% incidence of high-grade diarrhoea was found in the evaluated population (4.7% of patients treated with 5-FU-based therapy and 8.5% of patients treated with capecitabine-based CT). The overall incidence of high-grade diarrhoea observed was higher in the 1st and 2nd cycles (3.9%), with a subsequent sharp reduction from the 3rd cycle (1.3%) and negativisation from the 5th cycle. Lactobacillus kefiri LKF01 (Kefibios®) is safe and effective in preventing severe diarrhoea in cancer patients receiving 5-FU or capecitabine-based treatment.

The Effects of Probiotic Supplementation on the Incidence of Diarrhea in Cancer Patients Receiving Radiation Therapy: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

The protective effects of probiotic supplementation against radiation-induced diarrhea (RID) have been reported in previous systematic reviews; however so far, only non-conclusive results have been obtained. The objective of this study was to systematically update and evaluate the available evidence for probiotic supplementation. The protocol of this systematic review has been registered (CRD42018106059) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary efficacy outcome was the incidence of RID. Secondary outcomes were the incidence of watery stool, soft stool, and antidiarrheal medication use. There were eight trials, and a total of 1116 participants were included in the primary analysis. Compared with placebo, probiotics were associated with a lower risk of RID [risk ratio (RR) = 0.62, 95% CI = 0.46, 0.83]. A requisite heterogeneity-adjusted trial sequential analysis indicated conclusive evidence for this beneficial effect. No statistically significant reduction in RID (RR = 0.52, 95% CI = 0.14, 1.91) was observed on subgroup analysis in patients receiving both radiation therapy and chemotherapy. However, those patients receiving only radiation therapy (RT) demonstrated significant benefit (RR = 0.61, 95% CI = 0.48, 0.78). There was a significant difference in the antidiarrheal medication use (RR = 0.54, 95% CI = 0.35, 0.84) observed with the use of probiotics. However, no significant difference was observed for the incidence of soft and watery stool. The use of probiotics is beneficial in preventing RID in patients receiving RT.

Can an amino acid-based oral rehydration solution be effective in managing immune therapy-induced diarrhea?

Immune checkpoint inhibitor (ICPi) therapy has transformed the way we treat cancer. However, its immune related adverse events (irAEs) can be debilitating and life threatening. Immune therapy-induced diarrhea (ITID) is one of the most commonly encountered irAEs and can lead to expensive and prolonged hospitalizations. The current standard of care for grade 3 or 4 ITID involves ICPi discontinuation, the initiation of steroids, and infliximab for refractory disease. This treatment regimen reverses the desired anti-tumor effect of ICPis, can lead to side effects, and is cost-ineffective. We report the first case of the successful treatment of grade 3 ITID with steroids and an amino acid-based oral rehydration solution (AA-ORS), enterade. Research suggests that AA-ORS may be used to reduce diarrhea and adequately hydrate patients, in contrast to glucose-based oral rehydration solutions, which have been implicated as a contributing factor to diarrhea in cancer patients. We hypothesize that an AA-ORS may mitigate ITID via safer and more economically viable means than the current standard of care, but more controlled trials are needed to test this hypothesis.

Diarrhea With HER2-Targeted Agents in Cancer Patients: A Systematic Review and Meta-Analysis.

To fully investigate the diarrhea of human epidermal growth factor receptor 2 (HER2)-targeted agents in cancer patients. The relevant studies of the randomized, controlled trials (RCTs) in cancer patients treated with HER2-targeted agents were retrieved, and the systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until August 2018. Forty-two RCTs and 21633 patients were included. The current meta-analysis suggested that the use of HER2-targeted agents significantly increases the risk of developing all-grade diarrhea (RR, 2.78; 95%CI, 2.37-3.25; P < .00001) and high-grade diarrhea (RR, 4.89; 95%CI, 3.09-7.75; P < .00001). The RRs of all-grade diarrhea and high-grade diarrhea varied significantly according to drug type, control group, and treatment regimen. The RR of all-grade diarrhea varied significantly according to tumor type. Afatinib and neratinib tended to associate with the highest risk of all-grade diarrhea and high-grade diarrhea, respectively. Trastuzumab was associated with the lowest risk of diarrhea. Breast cancer patients tended to have a higher risk of all-grade diarrhea than patients with nonbreast cancer when receiving a HER2-targeted agent. The available data suggested that the use of HER2-targeted agents is associated with a significantly increased risk of diarrhea in cancer patients.

Infections caused by Clostridium difficile in cancer patients

The purpose of the studywas to determine the role of antibiotics as a risk factor of Clostridium difficile-associated diarrhea in hospitalized cancer patients.Material and Methods. The study included 844 hospitalized cancer patients with diarrhea. The presence of Clostridium difficile toxins A and B in the fecal samples was determined by enzyme immunoassay.Results.Clostridium difficile toxins A and B were detected in 100 cancer patients (42 % men and 58 % women). The incidence of Clostridium difficile-associated diarrhea was higher in women than in men (р&lt;0.02). Patients with hemoblastosis and gastrointestinal tumors were more susceptible to the development of Clostridium difficile associated diarrhea (p&lt;0.02). The use of cephalosporin antibiotics was the main risk factor (р&lt;0.001). In our study, 46 % of the patients took antibiotics.Conclusion.Clostridium difficile was shown to play a significant role in the development of diarrhea in cancer patients, and early detection of Clostridium difficile infection contributes to the early onset of therapy.

Diarrhea with epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients: A meta-analysis of randomized controlled trials.

We performed an meta-analysis to fully investigate the diarrhea of EGFR-TKIs in cancer patients. The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with EGFR-TKIs were retrieved and the systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published till August 2017. The relevant RCTs in cancer patients treated with EGFR-TKIs were retrieved and the systematic evaluation was conducted. Twenty-four RCTs and 13,748 patients were included. The current analysis suggested that the use of EGFR-TKIs increased the risk of all-grade diarrhea (RR 3.45; 95%CI, 2.94-4.06; p＜0.00001) and high-grade (≥grade 3) diarrhea (RR 8.22；95%CI, 6.02-11.23; p＜0.00001). On subgroup analysis, the risk of all-grade and high-grade diarrhea varied significantly within drug type. The risk of all-grade diarrhea varied significantly according to cancer type, whereas the risk of high-grade diarrhea did not. The risk of all-grade and high-grade diarrhea did not varied significantly based on treatment line, treatment duration and median age. The available data suggested that the use of EGFR-TKIs is associated with a significantly increased risk of diarrhea in cancer patients.

Effects of Aerobic and Resistance Exercises on Physical Symptoms in Cancer Patients: A Meta-analysis.

Objective. This study aimed to conduct a meta-analysis to establish the effect of exercise interventions on physical symptoms, including fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, and diarrhea in cancer patients and survivors. Methods. We searched articles published before April 2017 using the following databases: Cochrane Library, PubMed/MEDLINE, CINAHL, Scopus, PEDro, Health & Medical Collection, and Psychology Database. Randomized controlled trials (RCTs) of exercise intervention in cancer patients, which evaluated cancer-related physical symptoms using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, were included. Symptom scale data were extracted for meta-analysis. Subgroup analyses were performed for exercise types (aerobic, resistance, and mixed exercise programs). Results. Of the 659 articles, 10 RCTs were included in the meta-analysis, of which the mean PEDro score was 5.43 (SD = 1.28). Fatigue, pain, dyspnea, and insomnia were significantly lower in the intervention group than in the control group at postintervention in cancer patients. However, exercise intervention did not promote or suppress nausea/vomiting, loss of appetite, constipation, and diarrhea in cancer patients. The effect of exercise type on each symptom was not different. Conclusion. Exercise intervention was confirmed to improve fatigue, pain, and insomnia and might have reduced dyspnea in cancer patients. However, the benefits of exercise on nausea/vomiting, loss of appetite, constipation, and diarrhea were not shown in any exercise type. Further research is warranted to examine the effects of exercise interventions on physical symptoms in cancer patients.

1682O_PR - 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

1682O_PR - 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

Population exposure-safety analysis of cediranib for Phase I and II studies in patients with cancer.

A multistudy analysis of cediranib, a potent, selective inhibitor of all three vascular endothelial growth factor receptors (VEGFR-1, -2 and -3), was conducted to establish population exposure-safety models for the relationship of cediranib exposure to the safety endpoints, diastolic and systolic blood pressure (DBP and SBP) and diarrhoea in cancer patients. These models were applied to predict safety outcomes for different cediranib dose regimens. Models for hypertension and diarrhoea were constructed based on data from 10 Phase I and three Phase II studies comprising 631 cancer patients following cediranib once-daily oral dosing. Daily DBP and SBP were simultaneously characterized using indirect response models for predicted cediranib concentration-time courses, while daily diarrhoea events were modelled as ordered categorical variables with a proportional odds model with a Markov element for predicted average cediranib concentrations. For 20mg cediranib once-daily oral administration, the mean increase in DBP and SBP was predicted to be 7 (95% CI 3-13) and 8mmHg (95% CI 3-16), respectively, while the probability of mild diarrhoea, but not the severity, was predicted to increase over time. Severe diarrhoea was predicted to be resolved rapidly upon discontinuation of cediranib treatment. Maximum blood pressure increase was observed within the first few days of cediranib treatment, consistent with the pharmacokinetic profile of cediranib reaching steady state in about 5 days. The probability of diarrhoea increased with cediranib concentration but was far more dependent on the status of diarrhoea predicted on the previous day.

Biegunka u pacjentów z nowotworem

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Badian M, Dzierżanowski T. Diarrhea in cancer patients. Medycyna Paliatywna/Palliative Medicine. 2018;10(2):49-55. doi:10.5114/pm.2018.79793. APA Badian, M., & Dzierżanowski, T. (2018). Diarrhea in cancer patients. Medycyna Paliatywna/Palliative Medicine, 10(2), 49-55. https://doi.org/10.5114/pm.2018.79793 Chicago Badian, Magdalena, and Tomasz Dzierżanowski. 2018. "Diarrhea in cancer patients". Medycyna Paliatywna/Palliative Medicine 10 (2): 49-55. doi:10.5114/pm.2018.79793. Harvard Badian, M., and Dzierżanowski, T. (2018). Diarrhea in cancer patients. Medycyna Paliatywna/Palliative Medicine, 10(2), pp.49-55. https://doi.org/10.5114/pm.2018.79793 MLA Badian, Magdalena et al. "Diarrhea in cancer patients." Medycyna Paliatywna/Palliative Medicine, vol. 10, no. 2, 2018, pp. 49-55. doi:10.5114/pm.2018.79793. Vancouver Badian M, Dzierżanowski T. Diarrhea in cancer patients. Medycyna Paliatywna/Palliative Medicine. 2018;10(2):49-55. doi:10.5114/pm.2018.79793.

Application of a combination of a knowledge-based algorithm and 2-stage screening to hypothesis-free genomic data on irinotecan-treated patients for identification of a candidate single nucleotide polymorphism related to an adverse effect.

Interindividual variation in a drug response among patients is known to cause serious problems in medicine. Genomic information has been proposed as the basis for “personalized” health care. The genome-wide association study (GWAS) is a powerful technique for examining single nucleotide polymorphisms (SNPs) and their relationship with drug response variation; however, when using only GWAS, it often happens that no useful SNPs are identified due to multiple testing problems. Therefore, in a previous study, we proposed a combined method consisting of a knowledge-based algorithm, 2 stages of screening, and a permutation test for identifying SNPs. In the present study, we applied this method to a pharmacogenomics study where 109,365 SNPs were genotyped using Illumina Human-1 BeadChip in 168 cancer patients treated with irinotecan chemotherapy. We identified the SNP rs9351963 in potassium voltage-gated channel subfamily KQT member 5 (KCNQ5) as a candidate factor related to incidence of irinotecan-induced diarrhea. The p value for rs9351963 was 3.31×10−5 in Fisher's exact test and 0.0289 in the permutation test (when multiple testing problems were corrected). Additionally, rs9351963 was clearly superior to the clinical parameters and the model involving rs9351963 showed sensitivity of 77.8% and specificity of 57.6% in the evaluation by means of logistic regression. Recent studies showed that KCNQ4 and KCNQ5 genes encode members of the M channel expressed in gastrointestinal smooth muscle and suggested that these genes are associated with irritable bowel syndrome and similar peristalsis diseases. These results suggest that rs9351963 in KCNQ5 is a possible predictive factor of incidence of diarrhea in cancer patients treated with irinotecan chemotherapy and for selecting chemotherapy regimens, such as irinotecan alone or a combination of irinotecan with a KCNQ5 opener. Nonetheless, clinical importance of rs9351963 should be further elucidated.

Incidence and risk of diarrhea in cancer patients treated with pertuzumab: Evidence from published studies.

e22216 Background: Pertuzumab is a novel HER2 dimerization inhibitor administered in combination with trastuzumab and docetaxel in the treatment of HER2-positive metastatic breast cancer. Diarrhea ...

Altered irinotecan pharmacokinetics in diet‐induced obesity (1052.6)

Irinotecan (CPT‐11) is a topoisomerase I inhibitor which is highly effective in treatment of variety of cancers. It was found that patients with a BMI&gt;25 were twice as much susceptible to developing irinotecan‐induced liver toxicity than patients with BMI&lt;25. CPT‐11 is metabolized to SN‐38, which then undergoes glucuronidation by uridine glucuronosyl transferase (Ugt)1a1 to form SN‐38 glucuronide (SN‐38G). Excess accumulation of the toxic metabolite SN‐38 is known to cause fatal diarrhea in cancer patients. We hypothesize that reduction in Ugt1a1‐mediated SN‐38 glucuronidation causes SN‐38 accumulation leading to liver toxicity in obesity. Metabolism studies in liver S9 fractions showed that the rate of formation of SN‐38G was 2‐fold lower in the diet‐induced obese (DIO) mice compared to the lean controls. Pharmacokinetic studies showed plasma exposure of SN‐38 increased while that of SN‐38G decreased by 2‐folds in the DIO mice as compared to the lean controls. This corresponded with reduced expression of Ugt1a1 in DIO mice livers. We also observed significantly higher mRNA and serum levels of TNFα in the DIO mice as compared to the lean mice. Higher TNFα levels are known to be associated with liver toxicity. Thus, CPT‐11 dosage should be closely monitored for effective and safe chemotherapy in obese patients who are at a higher risk of developing liver toxicity.

Mechanisms of TKI-induced diarrhea in cancer patients

Tyrosine kinase inhibitors (TKIs) are increasingly common treatments for cancer; however, their effective use is hampered by unwanted side effects. One of the most common of these is TKI-induced diarrhea, although so far very little is known about its mechanisms and the best management approaches. As such, this review will briefly cover the extent of the problem, models for researching the problem and touch on future directions for management approaches to the problem. As there is a paucity of knowledge regarding the mechanisms of TKI-induced diarrhea in humans, this review will discuss the rodent models that have been used in the investigation of TKI-induced gut injury. This will be put into context with the pharmacological targets of TKIs and how this new information might help to better tailor treatment and management of patients on these drugs. The recognition of TKI-induced diarrhea as a significant treatment side effect has prompted efforts into uncovering the pathogenesis of this complication. This will enable future patients to be better managed throughout their treatment with these highly effective cancer drugs.