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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 -
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 -
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 -
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 -
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 -
Drug Development Research Aug 2023This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the... (Review)
Review
This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the development of new TNBC chemotherapy sensitivity biomarkers and therapeutic targets. The PubMed, Embase, Web of Knowledge, Cochrane Library, and four Chinese databases were searched up to January 27, 2023, and studies related to TNBC chemoresistance were included. The basic characteristics of the studies and the mechanisms of circRNAs in regulating TNBC chemoresistance were analyzed. A total of 28 studies published between 2018 and 2023 were included, and the chemotherapeutics included adriamycin, paclitaxel, docetaxel, 5-fluorouracil, lapatinib, and so forth. A total of 30 circRNAs were identified, 86.67% (n = 26) of these circRNAs were reported to act as microRNA (miRNA) sponges to regulate chemotherapy sensitivity, while only two circRNAs (circRNA-MTO1 and circRNA-CREIT) interacted with proteins. A total of 14, 12, and 2 circRNAs were reported to be associated with chemoresistance to adriamycin, taxanes, and 5-fluorouracil, respectively. Six circRNAs were found to act as miRNA sponges that promote chemotherapy resistance by regulating the PI3K/Akt signalling pathway. CircRNAs participate in the regulation of TNBC chemoresistance and can be used as biomarkers and therapeutic targets for improving chemotherapy sensitivity. However, further studies are needed to confirm the role of circRNAs in TNBC chemoresistance.
Topics: Humans; RNA, Circular; Triple Negative Breast Neoplasms; Drug Resistance, Neoplasm; Phosphatidylinositol 3-Kinases; MicroRNAs; Biomarkers; Doxorubicin; Fluorouracil; Gene Expression Regulation, Neoplastic
PubMed: 37114737
DOI: 10.1002/ddr.22069 -
European Journal of Clinical... Nov 2023This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL). (Review)
Review
PURPOSE
This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL).
METHODS
The PubMed, Scopus, Web of Science core collection, and Embase databases were searched until July 3, 2022. We included published full economic evaluation studies on BV for treating patients with HL. The methodological quality of the studies was assessed using the Quality of Health Economic Studies (QHES) checklist. Meanwhile, we used qualitative synthesis to analyze the findings. We converted the incremental cost-effectiveness ratios (ICERs) to the value of the US dollar in 2022.
RESULTS
Eight economic evaluations met the study's inclusion criteria. The results of three studies that compared BV plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) front-line therapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) showed that BV is unlikely to be cost-effective as a front-line treatment in patients advanced stage (III or IV) HL. Four studies investigated the cost-effectiveness of BV in patients with relapsed or refractory (R/R) HL after autologous stem cell transplantation (ASCT). BV was not cost-effective in the reviewed studies at accepted thresholds. In addition, the adjusted ICERs ranged from $65,382 to $374,896 per quality-adjusted life-year (QALY). The key drivers of cost-effectiveness were medication costs, hazard ratio for BV, and utilities.
CONCLUSION
Available economic evaluations show that using BV as front-line treatment or consolidation therapy is not cost-effective based on specific ICER thresholds for patients with HL or R/R HL. To decide on this orphan drug, we should consider other factors such as existence of alternative treatment options, clinical benefits, and disease burden.
Topics: Humans; Hodgkin Disease; Brentuximab Vedotin; Cost-Benefit Analysis; Hematopoietic Stem Cell Transplantation; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Vinblastine; Dacarbazine; Transplantation, Autologous
PubMed: 37656182
DOI: 10.1007/s00228-023-03557-6 -
The Lancet. Haematology Apr 2020Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of... (Meta-Analysis)
Meta-Analysis
Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis.
BACKGROUND
Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen.
METHODS
We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3-4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex.
FINDINGS
Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5-52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3-4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81-2·93; heterogeneity test Q=326·21; τ=0·0042; I=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25-7·65; heterogeneity test Q=527·33; τ=0·0384; I=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82-2·65) to 11·72% (3·00-24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting.
INTERPRETATION
The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages.
FUNDING
None.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Non-Hodgkin; Prednisone; Rituximab; Severity of Illness Index; Vincristine
PubMed: 32135128
DOI: 10.1016/S2352-3026(20)30031-4 -
Future Oncology (London, England) Feb 2022To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). A systematic literature review was conducted in November 2020 following best practice...
To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). A systematic literature review was conducted in November 2020 following best practice methodology. Fifty-five clinical studies were included, mostly investigating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or 'CHOP-like' regimens, with combination regimens showing similar effectiveness to CHOP alone. Aside from the combination of brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP), other available treatments showed no statistically significant benefit over CHOP in terms of overall or progression-free survival in overall PTCL patients. The mean monthly cost per patient in the USA ranged from 6328 to US$9356 based on six studies. One economic evaluation demonstrated A+CHP to be a more cost-effective treatment option than CHOP. Further research is needed to understand the humanistic and cost impact of frontline treatment for PTCL and its specific subtypes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Cost of Illness; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, T-Cell, Peripheral; Male; Prednisone; Treatment Outcome; Vincristine
PubMed: 34851173
DOI: 10.2217/fon-2021-1032