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Cancer Cell International May 2023Although doxorubicin chemotherapy is commonly applied for treating different malignant tumors, cardiotoxicity induced by this chemotherapeutic agent restricts its... (Review)
Review
PURPOSE
Although doxorubicin chemotherapy is commonly applied for treating different malignant tumors, cardiotoxicity induced by this chemotherapeutic agent restricts its clinical use. The use of silymarin/silibinin may mitigate the doxorubicin-induced cardiac adverse effects. For this aim, the potential cardioprotective effects of silymarin/silibinin against the doxorubicin-induced cardiotoxicity were systematically reviewed.
METHODS
In this study, we performed a systematic search in accordance with PRISMA guideline for identifying all relevant studies on "the role of silymarin/silibinin against doxorubicin-induced cardiotoxicity" in different electronic databases up to June 2022. Sixty-one articles were obtained and screened based on the predefined inclusion and exclusion criteria. Thirteen eligible papers were finally included in this review.
RESULTS
According to the echocardiographic and electrocardiographic findings, the doxorubicin-treated groups presented a significant reduction in ejection fraction, tissue Doppler peak mitral annulus systolic velocity, and fractional shortening as well as bradycardia, prolongation of QT and QRS interval. However, these echocardiographic abnormalities were obviously improved in the silymarin plus doxorubicin groups. As well, the doxorubicin administration led to induce histopathological and biochemical changes in the cardiac cells/tissue; in contrast, the silymarin/silibinin co-administration could mitigate these induced alterations (for most of the cases).
CONCLUSION
According to the findings, it was found that the co-administration of silymarin/silibinin alleviates the doxorubicin-induced cardiac adverse effects. Silymarin/silibinin exerts its cardioprotective effects via antioxidant, anti-inflammatory, anti-apoptotic activities, and other mechanisms.
PubMed: 37165384
DOI: 10.1186/s12935-023-02936-4 -
Cancer Treatment Reviews Jul 2023Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Although platinum-based chemotherapy (CT) is considered the standard treatment for relapsed platinum-sensitive ovarian cancer, there is currently no standard treatment for these patients. We compared the effectiveness of modern and older therapies in relapsed platinum-sensitive, BRCA-wild type, and ovarian cancers using a network meta-analysis (NMA).
METHODS
A systematic search of PubMed, EMBASE, and Cochrane Library was performed up to October 31, 2022. Randomized controlled trials (RCT) that compared different second-line approaches were included. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS).
RESULTS
In total, 17 RCTs (n = 9405) comparing various strategies were included. The risk of death was significantly decreased with carboplatin + pegylated liposomal doxorubicin + bevacizumab compared to platinum-based doublet CT (hazard ratio [HR] = 0.59, 95%CI 0.35, 1). Various strategies, including secondary cytoreduction followed by platinum-based CT, carboplatin + pegylated liposomal doxorubicin + bevacizumab, and platinum-based CT with bevacizumab or cediranib, were better than platinum-based doublets alone for PFS.
CONCLUSIONS
This NMA showed that carboplatin + pegylated liposomal doxorubicin + bevacizumab seems to increase the efficacy of standard second-line CT. These strategies can be considered when treating patients with relapsed platinum-sensitive ovarian cancer without BRCA mutations. This study provides systematic comparative evidence for the efficacy of different second-line therapies for relapsed ovarian cancer.
Topics: Humans; Female; Network Meta-Analysis; Bevacizumab; Carboplatin; Neoplasm Recurrence, Local; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Doxorubicin; Platinum; Polyethylene Glycols; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37201444
DOI: 10.1016/j.ctrv.2023.102571 -
European Journal of Drug Metabolism and... Jul 2022Almost 15 years after the introduction of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) therapy, the mean... (Meta-Analysis)
Meta-Analysis
Systematic Review and Pharmacokinetic Meta-analysis of Doxorubicin Exposure in Transcatheter Arterial Chemoembolization and Doxorubicin-Eluted Beads Chemoembolization for Treatment of Unresectable Hepatocellular Carcinoma.
BACKGROUND
Almost 15 years after the introduction of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC) therapy, the mean peak plasma concentration (C) and area under the concentration-time curve (AUC) for doxorubicin have still not been systematically reviewed or meta-analyzed.
OBJECTIVE
To conduct a systematic review and meta-analysis of available data and establish a reference range for C and AUC of doxorubicin DEB-TACE and TACE, as well as explore the potential influence of microspheres' size and type on these parameters.
METHODS
PubMed, EMBASE, and Web of Science were searched from August 1992 through December 2021. Studies measuring exposure parameters among HCC patients treated with doxorubicin DEB-TACE without restriction on language were included. Two independent reviewers extracted and unified data sets for pooled estimate analysis. The quality of the evidence was assessed via the Grading of Recommendations Assessment, Development and Evaluation framework. The ClinPK Statement checklist and Newcastle-Ottawa Scale (NOS) were used to determine the quality of studies.
RESULTS
Out of 666 studies, 246 full-text were reviewed, and 8 studies entered the meta-analysis (120 patients). C and AUC of doxorubicin were 7.52-fold (95% CI 7.65 to 7.42-fold; P < 0.0001) and 1.91-fold (95% CI 1.95 to 1.88-fold; P = 0.0001) lower with DEB-TACE compared to TACE. Significant reduction in pooled standardized mean difference (SMD) of C and AUC was observed with DEB-TACE versus TACE in direct comparison analysis (- 2.93; 95% CI - 3.60 to - 2.26, P < 0.00001, and - 1.73 95% CI - 2.55 to - 0.91, P < 0.0001, respectively). Moreover, in DEB-TACE stratification analysis, small microspheres revealed higher C, AUC and tumor response rate as well as lower complication rate.
LIMITATION
The heterogeneity could not be completely addressed through sensitivity and stratification analysis.
CONCLUSION
This meta-analysis provides exposure parameters of doxorubicin and justifies the advantage of DEB-TACE over TACE in terms of safety for patients with unresectable HCC. This study showed a marked association between the size of microsphere and exposure parameters of doxorubicin supporting the preference for small microspheres in DEB-TACE. The moderate and low quality of evidence is assigned to the C and AUC, respectively.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Humans; Liver Neoplasms; Microspheres
PubMed: 35543895
DOI: 10.1007/s13318-022-00762-z -
Medicine Nov 2023There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There have been controversial findings from recent studies regarding anthracyclines use and the subsequent risk of arrhythmias. This study aimed to evaluate the existing evidence of the risk of arrhythmias in patients treated with anthracyclines.
METHODS
PubMed, Scopus, and Web of Science databases were searched up to April 2022 using keywords such as "anthracycline" and "arrhythmia." Dichotomous data were presented as relative risk (RR) and confidence interval (CI), while continuous data were presented as mean difference (MD) and CI. Revman software version 5.4 was used for the analysis.
RESULTS
Thirteen studies were included with a total of 26891 subjects. Pooled analysis showed that anthracyclines therapy was significantly associated with a higher risk of arrhythmia (RR: 1.58; 95% CI: 1.41-1.76; P < .00001), ST segment and T wave abnormalities (RR: 1.73, 95% CI: 1.18-2.55, P = .005), conduction abnormalities and AV block (RR = 1.86, 95% CI = 1.06-3.25, P = .03), and tachycardia (RR: 1.736, 95% CI: 1.11-2.69, P = .02). Further analyses of the associations between anthracyclines and atrial flutter (RR = 1.30, 95% CI = 0.29-5.89, P = .74), atrial ectopic beats (RR: 1.27, 95% CI: 0.78-2.05, P = .34), and ventricular ectopic beats (RR: 0.93, 95% CI: 0.53-1.65, P = .81) showed no statistically significant results. Higher doses of anthracycline were associated with a higher risk of arrhythmias (RR: 1.49; 95% CI: 1.08-2.05; P = .02) compared to the lower doses (RR: 1.36; 95% CI: 1.00-1.85; P = .05). Newer generations of Anthracycline maintained the arrhythmogenic properties of previous generations, such as Doxorubicin.
CONCLUSION
Anthracyclines therapy was significantly associated with an increased risk of arrhythmias. Accordingly, Patients treated with anthracyclines should be screened for ECG abnormalities and these drugs should be avoided in patients susceptible to arrhythmia. The potential benefit of the administration of prophylactic anti-fibrotic and anti-arrhythmic drugs should also be explored.
Topics: Humans; Anthracyclines; Arrhythmias, Cardiac; Antibiotics, Antineoplastic; Doxorubicin; Tachycardia; Leukemia, Myeloid, Acute
PubMed: 37986405
DOI: 10.1097/MD.0000000000035770 -
European Journal of Pharmacology Aug 2021The safe development of nanotechnology and usage of nanoparticles (NPs) require the cellular toxicity examination of these NPs. Systematic studies are necessary to...
The safe development of nanotechnology and usage of nanoparticles (NPs) require the cellular toxicity examination of these NPs. Systematic studies are necessary to collect related data and comparison of the physicochemical features of NPs and their effects on cellular viability on model systems. In the present study, we systematically reviewed original studies, which investigated the cytotoxic effects and apoptosis of free NPs (loaded with doxorubicin (Dox)/or methotrexate (MTX)) via in vitro models. Articles were systematically collected by screening the literature published online in the following databases; PUBMED and SCOPUS and Web of Science and EMBASE. 23 in vitro cytotoxicity studies with 8 apoptosis examinations were found on osteosarcoma (OS) cell lines (mostly on MG-63). 43.47% of the synthesized NPs (10 studies) showed no cytotoxicity to OS cells. 39.13% of the synthesized NPs (9 studies) showed time and/or concentration related-cytotoxicity. Potent cytotoxic synthesized NP did not state. Significance difference between the half-maximal inhibitory concentration (IC50) of drug and drug/NP reported in all studies. Involved NPs in this systematic review for delivery of Dox/or MTX to OS cells have higher safety index and biocompatibility, although small and positively charged NPs acted more toxic in comparison to larger and negative ones, apoptosis rate like cytotoxicity index was notable in drug/NP group, to apply them in clinical works. Future studies are required to address the mechanisms involved in cytotoxicity and apoptosis with a special focus on in vivo investigations.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Death; Doxorubicin; Drug Delivery Systems; Humans; Methotrexate; Nanoparticles; Osteosarcoma
PubMed: 33933464
DOI: 10.1016/j.ejphar.2021.174131 -
Current Oncology (Toronto, Ont.) Aug 2014We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We... (Review)
Review
We conducted a systematic review to determine the appropriate use of bortezomib alone or in combination with other agents in patients with multiple myeloma (mm). We searched medline, embase, the Cochrane Library, conference proceedings, and the reference lists of included studies. We analyzed randomized controlled trials and systematic reviews if they involved adult mm patients treated with bortezomib and if they reported on survival, disease control, response, quality of life, or adverse effects. Twenty-six unique studies met the inclusion criteria. For patients with previously untreated mm and for candidates for transplantation, we found a statistically significant benefit in time to progression [hazard ratio (hr): 0.48, p < 0.001; and hr: 0.63, p = 0.006, respectively] and a better response with a bortezomib than with a non-bortezomib regimen (p < 0.001). Progression-free survival was longer with bortezomib and thalidomide than with thalidomide alone (p = 0.01). In non-candidates for transplantation, a significant benefit in overall survival was observed with a bortezomib regimen (hr compared with a non-bortezomib regimen: 0.61; p = 0.008), and in transplantation candidates receiving bortezomib, the response rate was improved after induction (p = 0.004) and after a first transplant (p = 0.016). In relapsed or refractory mm, overall survival (p = 0.03), time to progression (hr: 1.82; p = 0.000004), and progression-free survival (hr: 1.69; p = 0.000026) were significantly improved with bortezomib and pegylated liposomal doxorubicin (compared with bortezomib alone), and bortezomib monotherapy was better than dexamethasone alone (hr: 0.77; p = 0.027). Bortezomib combined with thalidomide and dexamethasone was better than either bortezomib monotherapy or thalidomide with dexamethasone (p < 0.001). In previously untreated or in relapsed or refractory mm patients, bortezomib-based therapy has improved disease control and, in some patients, overall survival.
PubMed: 25089109
DOI: 10.3747/co.21.1798 -
Translational Oncology Jul 2024Doxorubicin (DOX) a chemotherapy drug often leads to the development of resistance, in cancer cells after prolonged treatment. Recent studies have suggested that using... (Review)
Review
INTRODUCTION
Doxorubicin (DOX) a chemotherapy drug often leads to the development of resistance, in cancer cells after prolonged treatment. Recent studies have suggested that using metformin plus doxorubicin could result in synergic effects. This study focuses on exploring the co-treat treatment of doxorubicin and metformin for various cancers.
METHOD
Following the PRISMA guidelines we conducted a literature search using different databases such as Embase, Scopus, Web of Sciences, PubMed, Science Direct and Google Scholar until July 2023. We selected search terms based on the objectives of this study. After screening a total of 30 articles were included.
RESULTS
The combination of doxorubicin and metformin demonstrated robust anticancer effects, surpassing the outcomes of monotherapy drug treatment. In vitro experiments consistently demonstrated inhibition of cancer cell growth and increased rates of cell death. Animal studies confirmed substantial reductions in tumor growth and improved survival rates, emphasizing the synergistic impact of the combined therapy. The research' discoveries collectively emphasize the capability of the co-treat doxorubicin-metformin as a compelling approach in cancer treatment, highlighting its potential to address medicate resistance and upgrade generally helpful results.
CONCLUSION
The findings of this study show that the combined treatment regimen including doxorubicin and metformin has significant promise in fighting cancer. The observed synergistic effects suggest that this combination therapy could be valuable, in a setting. This study highlights the need for clinical research to validate and enhance the application of the doxorubicin metformin regimen.
PubMed: 38636389
DOI: 10.1016/j.tranon.2024.101946 -
European Journal of Surgical Oncology :... Dec 2023PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a... (Review)
Review
BACKGROUND
PIPAC consists in delivering normothermic chemotherapy solution directly into the peritoneal cavity as an aerosol under pressure. Currently PIPAC is considered as a palliative treatment for patients suffering from non-resectable peritoneal carcinomatosis. We performed a SR to assess tolerance and response of this novel method among patient with OC.
METHODS
We searched electronic database PubMed, Embase, Web of Science, Clinical Trials.gov. We only included clinical studies reporting PIPAC with cisplatin and doxorubicin in patients with ovarian cancer.
RESULTS
This systematic review included 4 studies. In 3 studies all patients were pretreated with cytoreductive surgery, in 1 study surgery was performed in 8/34 (23 %) patients. Mean PCI at first PIPAC procedure ranged from 16.3 to 19.6. All studies reported the proportion of patients with ascites at the first PIPAC with a pooled rate of 48,3 %. Pooled rate of CTCAE Grade 3 toxicity calculated on the total number of PIPAC was 6 % and Grade 4 was 0.9 %. One study reported two cases of small bowel perforation related or potentially related to PIPAC. On study reported a cumulative survival after 400 days of 62 % and a mean actuarial survival time of all patients who underwent PIPAC of 442 days. In another study the mean time to progression was 144 days (95 % CI 122-168 days).
CONCLUSION
This systematic review demonstrated that PIPAC with cisplatin and doxorubicin appear to have a good safety profile with low toxicity and encouraging trend in terms of overall survival.
Topics: Humans; Female; Cisplatin; Percutaneous Coronary Intervention; Antineoplastic Combined Chemotherapy Protocols; Ovarian Neoplasms; Doxorubicin; Aerosols
PubMed: 37951158
DOI: 10.1016/j.ejso.2023.107250 -
BioFactors (Oxford, England) May 2022Although the chemotherapeutic drug, doxorubicin, is commonly used to treat various malignant tumors, its clinical use is restricted because of its toxicity especially... (Review)
Review
Although the chemotherapeutic drug, doxorubicin, is commonly used to treat various malignant tumors, its clinical use is restricted because of its toxicity especially cardiotoxicity. The use of curcumin may alleviate some of the doxorubicin-induced cardiotoxic effects. Especially, using the nano-formulation of curcumin can overcome the poor bioavailability of curcumin and enhance its physicochemical properties regarding its efficacy. In this study, we systematically reviewed the potential cardioprotective effects of nano-curcumin against the doxorubicin-induced cardiotoxicity. A systematic search was accomplished based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the identification of all relevant articles on "the role of nano-curcumin on doxorubicin-induced cardiotoxicity" in the electronic databases of Scopus, PubMed, and Web of Science up to July 2021. One hundred and sixty-nine articles were screened following a predefined set of inclusion and exclusion criteria. Ten eligible scientific papers were finally included in the present systematic review. The administration of doxorubicin reduced the body and heart weights of mice/rats compared to the control groups. In contrast, the combined treatment of doxorubicin and nano-curcumin increased the body and heart weights of animals compared with the doxorubicin-treated groups alone. Furthermore, doxorubicin could significantly induce the biochemical and histological changes in the cardiac tissue; however, coadministration of nano-curcumin formulation demonstrated a pattern opposite to the doxorubicin-induced changes. The coadministration of nano-curcumin alleviates the doxorubicin-induced cardiotoxicity through various mechanisms including antioxidant, anti-inflammatory, and antiapoptotic effects. Also, the cardioprotective effect of nano-curcumin formulation against doxorubicin-induced cardiotoxicity was higher than free curcumin.
Topics: Animals; Antioxidants; Apoptosis; Cardiotoxicity; Curcumin; Doxorubicin; Mice; Rats
PubMed: 35080781
DOI: 10.1002/biof.1823 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745