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Cancers Dec 2023Constipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly... (Review)
Review
BACKGROUND
Constipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC.
METHODS
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information about the prevalence, etiology, and treatment of ATAIC.
RESULTS
A total of 73 articles were included. The reported prevalence ranged from 0.8% to 86.6%. Six studies reported an ATAIC prevalence of over 50%. The prevalence rates of constipation of grades 3 and 4 ranged between 0 and 11%. The importance of enteric neuronal integrity in gastrointestinal function was reported. The articles with the highest levels of evidence in relation to ATAIC treatment obtained in this systematic review studied treatments with acupuncture, sweet potato, osteopath, probiotics, and moxibustion.
CONCLUSIONS
The prevalence of constipation in patients undergoing antitumoral treatment is very diverse. Studies specifically designed to report the prevalence of antineoplastic treatment-induced constipation are needed. The importance of enteric neuronal integrity in gastrointestinal function was described. Thus, neuroprotection could be an area of research for the treatment of chemotherapy-induced gastrointestinal disorders.
PubMed: 38201526
DOI: 10.3390/cancers16010099 -
RMD Open Jul 2023To summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis...
Systematic literature review informing the 2022 update of the EULAR recommendations for the management of ANCA-associated vasculitis (AAV): part 1-treatment of granulomatosis with polyangiitis and microscopic polyangiitis.
OBJECTIVE
To summarise and update evidence to inform the 2022 update of the EULAR recommendations for the management of antineutrophil cytoplasm antibody-associated vasculitis (AAV).
METHODS
A systematic literature review (SLR) was performed to identify current evidence regarding treatment of AAV. PubMed, EMBASE and the Cochrane library were searched from 1 February 2015 to 25 February 2022. The evidence presented here is focused on the treatment of granulomatosis with polyangiitis and microscopic polyangiitis.
RESULTS
3517 articles were screened and 175 assessed by full-text review. Ninety articles were included in the final evidence synthesis. Cyclophosphamide and rituximab (RTX) show similar efficacy for remission induction (level of evidence (LoE) 1a) but RTX is more effective in relapsing disease (LoE 1b). Glucocorticoid (GC) protocols with faster tapering result in similar remission rates but lower rates of serious infections (LoE 1b). Avacopan can be used to rapidly taper and replace GC (LoE 1b). Data on plasma exchange are inconsistent depending on the analysed trial populations but meta-analyses based on randomised controlled trials demonstrate a reduction of the risk of end-stage kidney disease at 1 year but not during long-term follow-up (LoE 1a). Use of RTX for maintenance of remission is associated with lower relapse rates compared with azathioprine (AZA, LoE 1b). Prolonged maintenance treatment results in lower relapse rates for both, AZA (LoE 1b) and RTX (LoE 1b).
CONCLUSION
This SLR provides current evidence to inform the 2022 update of the EULAR recommendations for the management of AAV.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Granulomatosis with Polyangiitis; Humans; Microscopic Polyangiitis; Cyclophosphamide; Rituximab; Glucocorticoids; Remission Induction
PubMed: 37479496
DOI: 10.1136/rmdopen-2023-003082 -
Neurological Sciences : Official... Sep 2023Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision.
METHODS
The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS).
RESULTS
After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%).
CONCLUSION
Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.
Topics: Humans; Cladribine; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Clinical Trials as Topic; Observational Studies as Topic
PubMed: 37062787
DOI: 10.1007/s10072-023-06794-w -
The Lancet. Oncology Jul 2023Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about... (Meta-Analysis)
Meta-Analysis
Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials.
BACKGROUND
Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours.
METHODS
The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591.
FINDINGS
We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (p=0·0019), higher volume of metastases (p=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (p=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival).
INTERPRETATION
The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes.
FUNDING
UK Medical Research Council and Prostate Cancer UK.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms; Androgen Antagonists; Disease-Free Survival; Hormones; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic
PubMed: 37414011
DOI: 10.1016/S1470-2045(23)00230-9 -
Blood Cancer Journal Sep 2023Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an... (Meta-Analysis)
Meta-Analysis
Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Bortezomib; Clinical Protocols; Cyclophosphamide
PubMed: 37679351
DOI: 10.1038/s41408-023-00916-5 -
PloS One 2023Psoriasis is a systemic immune-mediated chronic inflammatory skin disease; its systemic manifestations and periodic recurrence negatively affect a patient's quality of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis is a systemic immune-mediated chronic inflammatory skin disease; its systemic manifestations and periodic recurrence negatively affect a patient's quality of life. Inflammatory cytokines are known to have an important role in the onset and progression of psoriasis, however, data on the association between circulating inflammatory cytokines and psoriasis risk is inconclusive. Here, we explore the relevance of circulating proinflammatory factors to the pathogenesis of psoriasis using a meta-analysis.
OBJECTIVE
To explore the association between circulating levels of inflammatory factors and psoriasis to elucidate the mechanisms underlying psoriasis and improve clinical diagnosis and treatment.
METHODS
We systematically retrieved articles published in PubMed, EMBASE, the Cochrane Library and the Web of Science from the establishment of each database to January 2023. The standard mean difference (SMD) in cytokine levels of individuals with psoriasis and healthy controls was used to check for correlations between circulating inflammatory factor levels and psoriasis.
RESULTS
Fifty-seven studies, with data from 2838 patients, were retrieved and included in the meta-analysis. Eleven inflammatory factors were studied (circulating interleukin-2 (IL-2), IL-4, IL-12, IL-17, IL-18, IL-22, IL-23, IL-35, IL-36, transforming growth factor-beta (TGF-β) and gamma-interferon (IFN-γ)). Of these, IL-2 [SMD = 1.29 (95% CI: 0.61-1.97; P <0.001)], IL-17 [SMD = 0.71 (95% CI: 0.12-1.30; P = 0.018)], IL-18 [SMD = 1.27 (95% CI: 0.64-1.90; P <0.001)], and IFN-γ [SMD = 1.90 (95% CI: 1.27-2.52; P <0.001)] levels had significant correlations with psoriasis.
CONCLUSION
Increased serum concentrations of the circulating inflammatory cytokines IL-2, IL-17, IL-18 and IFN-γ were significantly correlated with psoriasis.
Topics: Humans; Cytokines; Interferon-gamma; Interleukin-17; Interleukin-18; Interleukin-2; Psoriasis; Quality of Life
PubMed: 37883350
DOI: 10.1371/journal.pone.0293327 -
Critical Reviews in Oncology/hematology Aug 2023Folate metabolism is a target for various chemotherapeutic drugs. Folate and its synthetic variant folic acid are B-vitamins. To what extent these vitamins impact... (Review)
Review
Folate metabolism is a target for various chemotherapeutic drugs. Folate and its synthetic variant folic acid are B-vitamins. To what extent these vitamins impact treatment tolerance in patients with cancer remains unclear. A systematic literature review was conducted on intake and status of folate and folic acid in relation to chemotherapy-induced toxicities in children and adults with cancer. A total of 6231 publications were identified, of which 40 publications met the inclusion criteria. In 12 out of 22 studies focusing on antifolates, a deficient folate status and lower folate and folic acid intake were associated with a higher risk of toxicities. In 8 out of 14 studies focusing on fluoropyrimidine treatments, a higher folate status and intake were associated with a higher risk of toxicities. These findings might explain interindividual differences in treatment tolerance and highlight the importance of evaluating nutritional status in oncology care.
Topics: Adult; Child; Humans; Folic Acid; Vitamin B Complex; Nutritional Status; Neoplasms; Antineoplastic Agents; Dietary Supplements
PubMed: 37353179
DOI: 10.1016/j.critrevonc.2023.104061 -
Breast Cancer Research and Treatment Nov 2023Breast cancer and its treatments may increase the risk of type 2 diabetes (T2D). We conducted a systematic review and meta-analysis to investigate the association... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Breast cancer and its treatments may increase the risk of type 2 diabetes (T2D). We conducted a systematic review and meta-analysis to investigate the association between breast cancer and the incidence of T2D overall, and according to breast cancer treatments.
METHODS
We searched PubMed, Embase and references of relevant papers for studies on breast cancer, breast cancer treatment, and subsequent T2D risk. Using random-effects models, we calculated effect estimates and associated 95% confidence intervals of the association between breast cancer, adjuvant breast cancer treatments (i.e., endocrine therapy (tamoxifen, aromatase inhibitors, and combined) and chemotherapy), and subsequent T2D. We used funnel plots to assess publication bias.
RESULTS
Among 15 eligible studies, 10 reported on T2D risk after breast cancer, chemotherapy, or endocrine therapy; five studies investigated more than one association. Compared with patients without breast cancer, those with breast cancer and those who received any endocrine therapy had elevated risk of incident T2D (EE = 1.23, 95% CI = 1.13-1.33 and EE = 1.23, 95% CI = 1.16-1.32, respectively). Among breast cancer patients only, the risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (EE = 1.28, 95% CI = 1.18-1.38). Due to few studies, analyses investigating T2D risk after treatment with aromatase inhibitors or chemotherapy were inconclusive.
CONCLUSION
Our findings suggest an elevated risk of T2D in breast cancer survivors, particularly after tamoxifen therapy. Further research is needed to determine the impact of aromatase inhibitors, and chemotherapy on the incidence of T2D after breast cancer.
Topics: Humans; Female; Breast Neoplasms; Incidence; Aromatase Inhibitors; Diabetes Mellitus, Type 2; Tamoxifen
PubMed: 37656235
DOI: 10.1007/s10549-023-07043-6 -
Alternative Therapies in Health and... Sep 2023Turmeric is a well-known herb that has been used in many traditional medicinal systems since ancient times. Turmeric roots contain hydrophobic polyphenols called... (Meta-Analysis)
Meta-Analysis
CONTEXT
Turmeric is a well-known herb that has been used in many traditional medicinal systems since ancient times. Turmeric roots contain hydrophobic polyphenols called curcuminoids, which have proven anti-inflammatory and antioxidant effects and are shown to be beneficial for the management of musculoskeletal health. Various products containing curcumin or turmeric extract are commercially available.
OBJECTIVE
This systematic review and meta-analysis of randomized clinical trials (RCTs) is intended to evaluate the effective dose, safety, and efficacy of commercial turmeric extract and curcumin supplements in musculoskeletal health.
DESIGN
The research team performed a systematic literature search of PubMed, Google Scholar, and Cochrane Library databases and conducted a meta-analysis according to PRISMA guidelines.
SETTING
Authors from India and USA contributed to this systematic review and meta-analysis.
RESULTS
The research team analyzed 21 prospective, randomized clinical studies, of which seven studies were focused on skeletal muscle health and fourteen on joint health. Statistical heterogeneity was established based on the results of heterogeneity analysis of a Chi-square (χ2) value for Cochran's Q statistic of 29.3765 for musculoskeletal and 3666.80 for joint health studies (P < .0001 for both analyses). Therefore, the random effects model was used. The χ2 value of the random effects model was 216.5545 for skeletal muscle health studies and 1400.65 for joint health studies, which was statistically significant with P < .0001 for both analyses.
CONCLUSIONS
Turmeric extract and curcumin supplements can be effective adjuvants for the management of musculoskeletal health, with a low incidence of AEs. The water-dispersible turmeric extract, WDTE60N, at a dose of 250 mg per day, was found to be more effective than other curcumin products. However, the studies included in the analysis were conducted using diverse doses and treatment durations. Further evaluation using comparisons in future clinical trials can establish the appropriate effective dose of curcumin supplements for the overall maintenance of musculoskeletal health.
Topics: Humans; Curcumin; Curcuma; Plant Extracts; Anti-Inflammatory Agents
PubMed: 37574203
DOI: No ID Found -
BMC Cancer Sep 2023Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main...
BACKGROUND
Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart.
METHODS
A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed.
RESULTS
Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor.
CONCLUSIONS
Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.
Topics: Humans; Adolescent; Child; Cardiotoxicity; Mitoxantrone; Neoplasms; Heart; Anthracyclines; Polyketides
PubMed: 37710224
DOI: 10.1186/s12885-023-11353-9