-
Journal of Cancer Research and... Dec 2021To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy, safety, and potential advantages of Poly (ADP-ribose) polymerase inhibitors (PARPi) in treating BRCA-mutated breast cancer, we performed a meta-analysis of published studies.
MATERIALS AND METHODS
Four randomized controlled trials (RCTs) were included in the meta-analysis. Data analysis was conducted in Review Manager 5.4.
RESULTS
The progression-free survival (PFS) of the patients with triple-negative (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.74-0.88; P < 0.00001) or hormone receptor-positive (HR 0.83; 95% CI 0.77-0.91; P < 0.0001) BRCA-mutated breast cancer was significantly extended in the containing PARPi therapy arm versus the chemotherapy arm. PFS of the patients who did not receive platinum-based therapy (HR 0.78; 95% CI 0.70-0.86; P < 0.0001) was significantly extended in the PARPi monotherapy arm versus the chemotherapy arm. The objective response rate of patients treated by PARPi monotherapy (risk ratio [RR] 2.51; 95% CI 1.81-3.47; P < 0.00001) was significantly higher than that of patients treated by chemotherapy. The incidence of thrombocytopenia in patients received PARPi combined therapy was obviously increased compared with chemotherapy group (RR 1.36; 95% CI 1.07-1.72; P = 0.01). PARPi monotherapy markedly increased the incidence of anemia (RR 5.83; 95% CI 2.64-12.88; P < 0.0001) versus chemotherapy. However, the risk of neutropenia (RR 0.48; 95% CI 0.29-0.81; P = 0.006) was reduced in the PARPi monotherapy arm. There were no statistical differences in other adverse events among these three groups.
CONCLUSIONS
PARPi combined therapy and monotherapy improved PFS of patients with BRCA-mutated breast cancer compared with standard chemotherapy, which was unrelated to type of BRCA mutation and status of hormone receptor. PARPi therapy has slightly higher hematological toxicity and better overall safety and tolerance.
PROSPERO REGISTRATION NUMBER
CRD42020204385.
Topics: Adenosine Diphosphate; Breast Neoplasms; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Ribose
PubMed: 35381738
DOI: 10.4103/jcrt.jcrt_2085_21 -
Frontiers in Oncology 2022Irinotecan is a first-line agent in the systematic treatment of colorectal cancer (CRC). Adjusting the dose of irinotecan according to the () genotype reflects the...
BACKGROUND
Irinotecan is a first-line agent in the systematic treatment of colorectal cancer (CRC). Adjusting the dose of irinotecan according to the () genotype reflects the principle of individualized and precision medicine, and may improve the chemotherapy response and survival of CRC.
METHODS
To summarize the feasibility, efficacy and safety of high dose irinotecan in CRC patients with wild-type or heterozygous alleles, PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials online databases were searched from the date of creation to October 22, 2021.
RESULTS
A total of 1,186 related literatures were searched, and 14 studies were included for review according to the inclusion criteria. The results indicated that the maximum tolerated dose of irinotecan in CRC patients with wild-type or heterozygous variant was significantly higher than the conventional recommended dose. Chemotherapy based on high dose irinotecan improved the clinical efficacy in mCRC patients with wild-type and heterozygous variant, and the toxicity was tolerated, as reflected in most studies.
CONCLUSIONS
We are optimistic about the application of high dose irinotecan for mCRC patients with wild-type or heterozygous variant, which will provide a relatively clear direction for future research and certain norms for clinical practice.
PubMed: 35356222
DOI: 10.3389/fonc.2022.854478 -
International Journal of Preventive... 2022Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy... (Review)
Review
BACKGROUND
Neonatal jaundice is a prevalent disease that causes many complications, including kernicterus and even death. Previous studies have shown that clofibrate as an aryloxy isobutyric acid derivate can be effectively applied for the treatment of neonatal jaundice. Thus, this review was carried out to investigate the effects and mechanism of action of clofibrate on neonatal jaundice.
METHODS
The keywords such as "Clofibrate" in combination with "Neonatal jaundice" or "Neonatal hyperbilirubinemia" or "Newborn Jaundice" were used to search for relevant publications indexed in the Institute for Scientific Information (ISI), Scopus, PubMed, and Google Scholar databases. Finally, after reviewing the studies, 24 papers were included in this study.
RESULTS
Results showed that the processes of albumin-bound bilirubin transfer to the hepatocytes, hepatic uptake, and storage via ligandin, hepatic conjugation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), conjugation into the bile via MRP2 represent the main action mechanism of clofibrate that turns it into the bilirubin conjugates and expels it from the bile. Besides, clofibrate has been shown to reduce the level of Total Serum Bilirubin (TSB) in infants even at a dosage of 25 mg/kg without leaving side effects.
CONCLUSIONS
The results of this review revealed that clofibrate effectively reduces TSB in short-term usage and can even have a promising effect at the dosage of 25 mg/kg in full-term infants. Most studies have shown this property over a short period in term infants, and there is no evidence about long-term usage in this regard.
PubMed: 35281975
DOI: 10.4103/ijpvm.IJPVM_407_20 -
Medicine Nov 2021There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.
METHODS
Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I2-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.
RESULTS
Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76-6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01-1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01-1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22-2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20-1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32-4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the "Publication year", "Country", "Sample size", and "Cutoff value" might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.
CONCLUSION
The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.
Topics: Adenocarcinoma of Lung; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Lymphatic Metastasis; NM23 Nucleoside Diphosphate Kinases; Neoplasm Grading; Neoplasm Staging; Prognosis
PubMed: 34964763
DOI: 10.1097/MD.0000000000027919 -
European Journal of Vascular and... Jan 2022Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.
OBJECTIVE
Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease.
METHODS
A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS
There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes.
CONCLUSION
ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.
Topics: Cause of Death; Clopidogrel; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Activation; Platelet Function Tests; Postoperative Complications; Postoperative Hemorrhage; Purinergic P2 Receptor Antagonists; Treatment Outcome
PubMed: 34844834
DOI: 10.1016/j.ejvs.2021.09.026 -
Frontiers in Pharmacology 2021Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However,...
Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However, the optimal choice of P2Y12 adenosine diphosphate receptor inhibitor in elderly (aged ≥65 years) patients remains controversial. We conducted a meta-analysis to compare the efficacy and safety of ticagrelor and clopidogrel in elderly patients with ACS. We comprehensively searched in Web of Science, EMBASE, PubMed, and Cochrane databases through 29 March, 2021 for eligible randomized controlled trials (RCTs) comparing the efficacy and safety of ticagrelor or clopidogrel plus aspirin in elderly patients with ACS. Four studies were included in the final analysis. A fixed effects model or random effects model was applied to analyze risk ratios (RRs) and hazard ratios (HRs) across studies, and I to assess heterogeneity. A total number of 4429 elderly patients with ACS were included in this analysis, of whom 2170 (49.0%) patients received aspirin plus ticagrelor and 2259 (51.0%) received aspirin plus clopidogrel. The ticagrelor group showed a significant advantage over the clopidogrel group concerning all-cause mortality (HR 0.78, 95% CI 0.63-0.96, I = 0%; RR 0.79, 95% CI 0.66-0.95, I = 0%) and cardiovascular death (HR 0.71, 95% CI 0.56-0.91, I = 0%; RR 0.76, 95% CI 0.62-0.94, I = 5%) but owned a higher risk of PLATO major or minor bleeding (HR 1.46, 95% CI 1.13-1.89, I = 0%; RR 1.40, 95% CI 1.11-1.76, I = 0%). Both the groups showed no significant difference regarding major adverse cardiovascular events (MACEs) (HR 1.06, 95% CI 0.68-1.65, I = 77%; RR 1.04, 95% CI 0.69-1.58, I = 77%). For elderly ACS patients, aspirin plus ticagrelor reduces cardiovascular death and all-cause mortality but increases the risk of bleeding. Herein, aspirin plus ticagrelor may extend lifetime for elderly ACS patients compared with aspirin plus clopidogrel. The optimal DAPT for elderly ACS patients may be a valuable direction for future research studies.
PubMed: 34721032
DOI: 10.3389/fphar.2021.743259 -
Critical Care Explorations Sep 2021Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy,... (Review)
Review
UNLABELLED
Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients.
DATA SOURCES
MEDLINE, PubMed Central, Embase, and CENTRAL.
STUDY SELECTION
Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021.
DATA EXTRACTION
Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison.
DATA SYNTHESIS
Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; = 0.030).
CONCLUSIONS
Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.
PubMed: 34549189
DOI: 10.1097/CCE.0000000000000526 -
Breast (Edinburgh, Scotland) Dec 2021This meta-analysis aimed to investigate the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in BRCA-mutated advanced breast... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aimed to investigate the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in BRCA-mutated advanced breast cancer patients comprehensively.
METHODS
We conducted a systematic literature research through PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), wanfang, China Biology Medicine disc (CBMdisc), and ClinicalTrials.gov from inception to January 2021. Randomized controlled trials (RCTs) with available data comparing PARP inhibitors versus control therapy in BRCA-mutated advanced breast cancer were eligible for analysis. Statistical analyses were performed with Review Manager (RevMan) version 5.4 and R version 4.0.3.
RESULTS
1706 studies were retrieved in total, and 4 RCTs with 1540 patients were eligible for meta-analysis finally. The results showed that progression-free survival (PFS) and overall survival (OS) were significantly improved in germline BRCA-mutated breast cancer patients with PARP inhibitors (HR 0.64, 95% CI [0.56-0.74]; HR 0.86, 95% CI [0.74-0.99], respectively) with no significant heterogeneity across studies (I = 22%, χ p = 0.28; I = 0%, χ p = 0.70, respectively). There was no significant difference in the overall adverse events (AEs), grade≥3 AEs and AEs leading to treatment discontinuation between PARP inhibitor arms and control arms (RR 1.01, 95% CI [0.99-1.02]; RR 0.95, 95% CI [0.83-1.09]; RR 1.17, 95% CI [0.87-1.57], respectively). Based on the available data, PARP inhibitors provided comparable or better results than control arms in improving the quality of life in BRCA-mutated advanced breast cancer patients.
CONCLUSIONS
PARP inhibitors prolonged PFS and OS among patients with BRCA-mutated advanced breast cancer with tolerable safety and improved quality of life.
Topics: Antineoplastic Agents; Breast Neoplasms; Female; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Progression-Free Survival
PubMed: 34455227
DOI: 10.1016/j.breast.2021.08.009 -
Journal of the National Cancer Institute Nov 2021Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity...
BACKGROUND
Loss of ovarian function is a recognized adverse effect of chemotherapy for breast cancer and of great importance to patients. Little is known about the ovarian toxicity of newer cancer treatments. This study examined whether breast cancer clinical trials include assessment of the impact of trial interventions on ovarian function.
METHODS
Eligible trials were phase III (neo)adjuvant trials of pharmacologic treatments for breast cancer, recruiting between June 2008 and October 2019, which included premenopausal women. MEDLINE, EMBASE, Clinicaltrials.gov, and EudraCT were searched. Data were extracted from trial publications, protocols, databases, and a survey sent to all trial chairs. Tests of statistical significance were 2-sided.
RESULTS
Of 2354 records identified, 141 trials were eligible. Investigational treatments included chemotherapy (36.9%), HER2 targeted (24.8%), endocrine (12.8%), immunotherapy (7.8%), cyclin-dependent kinase 4/6 inhibitors (5.0%), and poly-ADP-ribose polymerase inhibitors (2.8%). Ovarian function was a prespecified endpoint in 13 (9.2%) trials. Forty-five (31.9%) trials collected ovarian function data, but only 33 (23.4%) collected posttrial-intervention data. Common postintervention data collected included menstruation (15.6%), pregnancy (13.5%), estradiol (9.9%), and follicle-stimulating hormone levels (8.5%). Only 4 (2.8%) trials collected postintervention anti-müllerian hormone levels, and 3 (2.1%) trials collected antral follicle count. Of 22 trials investigating immunotherapy, cyclin-dependent kinase 4/6 inhibitors, or poly-ADP-ribose polymerase inhibitors, none specified ovarian function as an endpoint, but 4 (18.2%) collected postintervention ovarian function data.
CONCLUSIONS
The impact of pharmacologic interventions on ovarian function is infrequently assessed in phase III breast cancer (neo)adjuvant trials that include premenopausal women. Trialists should consider inclusion of ovarian function endpoints when designing clinical trials, given its importance for informed decision making.
Topics: Female; Humans; Pregnancy; Adenosine Diphosphate Ribose; Breast Neoplasms; Cyclin-Dependent Kinase 4; Ovary; Premenopause; Clinical Trials, Phase III as Topic
PubMed: 34048575
DOI: 10.1093/jnci/djab111 -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2