-
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 -
Urologic Oncology May 2022The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this systematic literature review and meta-analysis was to compare the pathological response rate and prognosis of the dose dense Methotrexate, vinblastine, doxorubicin and cisplatin (ddMVAC) regimen and gemcitabine and cisplatin (GC) regimen as neoadjuvant chemotherapy choices for bladder cancer.
METHODS
A literature review of articles published before February 28, 2021, was conducted using the PubMed, Web of Sciences and Embase databases. Data for comparison included pathological response rate and overall survival.
RESULTS
Five studies including 1,206 patients were identified and assessed for the meta-analysis. The pooled analysis yielded an odds ratio value of 1.29 (95% CI, 0.86-1.92) with a downstaging rate and an odds ratio value of 1.57 (95% CI, 1.10-2.25) with a complete response rate when comparing ddMVAC with the GC regimen. The pooled analysis yielded a hazard ratio of 0.47 (95% CI, 0.30-0.72) with regard to overall survival between the two regimens.
CONCLUSION
Compared with the GC regimen, ddMVAC has a better pathological response rate, especially the complete response rate, and provides longer overall survival as a neoadjuvant chemotherapy regimen for bladder cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Female; Humans; Male; Methotrexate; Neoadjuvant Therapy; Retrospective Studies; Urinary Bladder Neoplasms; Vinblastine
PubMed: 34949512
DOI: 10.1016/j.urolonc.2021.11.016 -
The Cochrane Database of Systematic... Mar 2018Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease.
OBJECTIVES
To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life.
SEARCH METHODS
We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017.
SELECTION CRITERIA
All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study.
MAIN RESULTS
We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone.
AUTHORS' CONCLUSIONS
Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Epirubicin; Fluorouracil; Humans; Paclitaxel; Pancreatic Neoplasms; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 29557103
DOI: 10.1002/14651858.CD011044.pub2 -
PloS One 2015The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results... (Meta-Analysis)
Meta-Analysis Review
The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity.
Topics: Antibiotics, Antineoplastic; Daunorubicin; Dose-Response Relationship, Drug; Humans; Leukemia, Myeloid, Acute; Prospective Studies
PubMed: 25993000
DOI: 10.1371/journal.pone.0125612 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021To investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS),... (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML).
METHODS
We searched published reports at the Medline, Embase, and Cochrane Databases as well as other databases from inception through July 2019. There was no restriction on date of publication or language (PROSPERO registration CRD42018095843).
RESULTS
We enrolled 12 randomized controlled trials that included data of 4583 AML patients whose disease was untreated or relapsed/refractory, and compared the CR, death during induction therapy, DFS, and OS between mitoxantrone and daunorubicin. Mitoxantrone significantly increased the CR rate (relative risk = 1.07; 95% confidence interval [CI], 1.01, 1.14; P = .03) and DFS (hazard ratio = 0.87; 95% CI, 0.79, 0.96; P = .005) compared to daunorubicin. However, there was no significant difference in death during induction therapy (relative risk = 1.00; 95% CI, 0.81, 1.24; P = .99) and OS (hazard ratio = 0.94; 95% CI, 0.87, 1.01; P = .077) between the two drugs.
CONCLUSION
Although more studies are needed to compare mitoxantrone with higher-dose daunorubicin, the results showed that compared to daunorubicin, mitoxantrone can significantly improve CR and DFS in patients of all ages. These findings suggest that mitoxantrone may be a better choice than daunorubicin as an induction chemotherapy agent for AML patients, especially in developing countries.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Randomized Controlled Trials as Topic
PubMed: 32863193
DOI: 10.1016/j.clml.2020.08.001 -
Journal of the American Heart... Sep 2021Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to... (Meta-Analysis)
Meta-Analysis
Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Exercise; Humans
PubMed: 34472371
DOI: 10.1161/JAHA.121.021580 -
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 -
World Journal of Urology Aug 2023The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank... (Meta-Analysis)
Meta-Analysis
Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.
PURPOSE
The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them.
METHODS
We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment.
RESULTS
Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options.
CONCLUSION
No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.
Topics: Humans; Cisplatin; Neoadjuvant Therapy; Methotrexate; Bayes Theorem; Network Meta-Analysis; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Urinary Bladder Neoplasms; Doxorubicin; Vinblastine; Cystectomy
PubMed: 37347252
DOI: 10.1007/s00345-023-04478-w -
Current Drug Metabolism 2018Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of... (Review)
Review
BACKGROUND
Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes.
METHODS
A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity.
RESULTS
Polymorphisms in the main enzymes of anthracyclines metabolism (CBR, AKR, NQO1, NOS3) have been related to lower enzymatic activity and higher cardiotoxicity. Moreover, variant alleles in the genes of carcinogens and chemotherapy neutralizing enzymes (GST, SULT, NADP(H) oxidase) have been associated with ROS generation and drug efficacy, influencing the survival rates and cardiac toxicities. In addition, genetic variability in the transporters of anthracyclines could affect the intake in cells, including influx (SLC28A3, SLC22A12, SLCO1B1) and efflux transporters (ABCB1, ABCC1, ABCC3, ABCG2).
CONCLUSION
The knowledge of the role of pharmacogenetics in anthracyclines metabolism could explain the differences observed in their disposition in leukemic cells. These genetic variants are proposed biomarkers in clinical practice in order to individualize chemotherapy schemes, potentially increasing the effectiveness and reducing the toxicities.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Humans; Leukemia, Myeloid, Acute; Pharmacogenetics; Polymorphism, Genetic
PubMed: 29090664
DOI: 10.2174/1389200218666171101124931 -
Metabolism: Clinical and Experimental Sep 2022Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents,... (Review)
Review
Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.
Topics: Animals; Antineoplastic Agents; Cardiotoxicity; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry
PubMed: 35809654
DOI: 10.1016/j.metabol.2022.155250