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Frontiers in Cardiovascular Medicine 2023Although chemotherapy agents are used to treating cancers, they have serious side effects, like their harmful effects on the cardiovascular system, limiting the clinical... (Review)
Review
AIMS
Although chemotherapy agents are used to treating cancers, they have serious side effects, like their harmful effects on the cardiovascular system, limiting the clinical use of these chemotherapy agents. This study aimed to systematically investigate the potential role of ginseng derivatives in the prevention of chemotherapy-induced cardiac toxicity.
METHODS
This systematic review was performed according to PRISMA guidelines strategy in databases till August 2022. First, identify studies related to using search terms in titles and abstracts. After studying and screening 209 articles, 16 articles were selected in this study according to our inclusion and exclusion criteria.
RESULTS
According to the findings of this study, ginseng derivatives showed significant changes in biochemical, histological, and heart weight loss, as well as a reduction in mortality, which occurred in the groups treated with chemotherapy agents compared to the control groups. Co-administration of ginseng derivatives with chemotherapy agents inhibited or reversed these changes to near-moderate levels. The protective effects of ginseng derivatives can be due to their anti-inflammatory, anti-oxidant, and anti-apoptotic action.
CONCLUSION
This systematic review shows evidence that concomitant administration of ginseng derivatives improves chemotherapy-induced cardiac toxicity. However, for better conclusions about the practical mechanisms of ginseng derivatives in reducing the cardiac toxic effects of chemotherapy agents and evaluating the efficacy and safety of the compound simultaneously, it is necessary to design comprehensive studies.
PubMed: 36844721
DOI: 10.3389/fcvm.2023.1022360 -
Reviews on Recent Clinical Trials 2023Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated with cardiomyopathy. This meta-analysis aimed to compare the effects of prophylactic agents for preventing cardiotoxicity induced following anticancer agents.
METHODS
In this meta-analysis, Scopus, Web of Science, and PubMed were surfed for articles published by December 30, 2020. The keywords were angiotensin-converting enzyme inhibitor (ACEI), enalapril, captopril, angiotensin receptor blocker, beta blocker, metoprolol, bisoprolol, isoprolol, statin, valsartan, losartan, eplerenone, idarubicin, nebivolol, dihydromyricetin, ampelopsin, spironolactone, dexrazoxane, antioxidants, cardiotoxicity, n-acetyl-tryptamine, cancer, neoplasms, chemotherapy, anthracyclines, doxorubicin, daunorubicin, epirubicin, idarubicin, ejection fraction or a combination of them in the titles or abstracts.
RESULTS
A total of 17 articles out of 728 studies examining 2,674 patients were included in this systematic review and meta-analysis. Ejection fraction (EF) values in the baseline, 6-month, and 12-month follow-up in the intervention group turned out to be 62.52 ± 2.48, 59.63 ± 4.85, and 59.42 ± 4.53, whereas in the control group appeared to be 62.81 ± 2.58, 57.69 ± 4.32, and 58.60 ± 4.58, respectively. Through comparison of the two groups, EF was found to increase in the intervention group by 0.40 after 6 months (Standardized mean difference (SMD): 0.40, 95% confidence interval (CI): 0.27, 0.54), thus proving higher than that of the control groups following the cardiac drugs.
CONCLUSION
This meta-analysis showed that prophylactic treatment with cardio-protective drugs, including dexrazoxane, beta blocker, and ACEI drugs in patients undergoing chemotherapy with anthracycline, have a protective effect on LVEF and prevent EF drop.
Topics: Humans; Cardiotoxicity; Dexrazoxane; Idarubicin; Antineoplastic Agents; Antibiotics, Antineoplastic; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Neoplasms; Adrenergic beta-Antagonists
PubMed: 36803186
DOI: 10.2174/1574887118666230118102252 -
BMC Cancer Dec 2022Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often...
BACKGROUND
Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often experience long-term toxicities. The main objective of this systematic review is to provide an overview of the discovery of novel associations of germline polymorphisms with treatment response and/or chemotherapy-induced toxicities in osteosarcoma. METHODS: MEDLINE and Embase were systematically searched (2010-July 2022). Genetic association studies were included if they assessed > 10 germline genetic variants in > 5 genes in relevant drug pathways or if they used a genotyping array or other large-scale genetic analysis. Quality was assessed using adjusted STrengthening the REporting of Genetic Association studies (STREGA)-guidelines. To find additional evidence for the identified associations, literature was searched to identify replication studies.
RESULTS
After screening 1999 articles, twenty articles met our inclusion criteria. These range from studies focusing on genes in relevant pharmacokinetic pathways to whole genome sequencing. Eleven articles reported on doxorubicin-induced cardiomyopathy. For seven genetic variants in CELF4, GPR35, HAS3, RARG, SLC22A17, SLC22A7 and SLC28A3, replication studies were performed, however without consistent results. Ototoxicity was investigated in one study. Five small studies reported on mucosistis or bone marrow, nephro- and/or hepatotoxicity. Six studies included analysis for treatment efficacy. Genetic variants in ABCC3, ABCC5, FasL, GLDC, GSTP1 were replicated in studies using heterogeneous efficacy outcomes.
CONCLUSIONS
Despite that results are promising, the majority of associations were poorly reproducible due to small patient cohorts. For the future, hypothesis-generating studies in large patient cohorts will be necessary, especially for cisplatin-induced ototoxicity as these are largely lacking. In order to form large patient cohorts, national and international collaboration will be essential.
Topics: Child; Adolescent; Humans; Pharmacogenetics; Ototoxicity; Osteosarcoma; Cisplatin; Bone Neoplasms
PubMed: 36536332
DOI: 10.1186/s12885-022-10434-5 -
Frontiers in Pharmacology 2022The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the...
Cardiovascular adverse events associated with cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone with or without rituximab ((R)-CDOP) in non-Hodgkin's lymphoma: A systematic review and meta-analysis.
The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the cardiotoxicity and efficacy of the (R)-CDOP regimen compared with conventional anthracyclines have not been demonstrated in the general population. Therefore, this systematic review and meta-analysis evaluated the risk of cardiotoxicity and efficacy associated with the (R)-CDOP regimen in patients with non-Hodgkin's lymphoma. PubMed, Embase, Cochrane Library, CNKI, WanFang Database, and VIP were searched. The search covered the period from the start of the clinical use of (R)-CDOP to April 2022. We searched the literature for cardiovascular adverse events associated with (R)-CDOP in non-Hodgkin's lymphoma. The data were analyzed using R 4.2.0 and Stata 12.0. From the included studies, the important findings were as follows: total cardiovascular event rate, 7.45% (95% confidence interval [CI] = 4.86%-10.44%); non-serious cardiovascular adverse event rate, 6.48% (95% CI = 3.70%-9.8%); serious cardiovascular adverse event rate, 0.67% (95% CI = 0.00%-2.12%); heart failure rate, 0.55% (95% CI = 0.00%-1.93%); rate of treatment discontinuation attributable to left ventricular dysfunction or heart failure, 0.02% (95% CI = 0.00%-0.57%); and cardiovascular death rate, 0.00% (95% CI = 0.00%-0.37%). Compared with the (R)-CHOP regimen, the (R)-CDOP regimen reduced the risk of cardiovascular events, including total cardiovascular adverse events (odds ratio [OR] = 0.161, 95% CI = 0.103-0.251, < 0.001, and NNT = 3.7), non-serious cardiovascular adverse events (OR = 0.171, 95% CI = 0.093-0.314, < 0.001, and NNT = 3.6), serious cardiovascular adverse events (OR = 0.252, 95% CI = 0.119-0.535, < 0.001, and NNT = 6.8), and heart failure (OR = 0.294, 95% CI = 0.128-0.674, = 0.004, and NNT = 9.5). To evaluate the survival benefits, we compared (R)-CDOP and (R)-CHOP regimens. We found that the (R)-CDOP regimen was no less efficacious, including complete remission (CR) (OR = 1.398, 95% CI = 0.997-1.960, and = 0.052), partial response (PR) (OR = 1.631, 95% CI = 1.162-2.289, and = 0.005), objective response rate (ORR) (OR = 2.236, 95% CI = 1.594-3.135, and < 0.001), stable disease (SD) (OR = 0.526, 95% CI = 0.356-0.776, and = 0.001), and progressive disease (PD) (OR = 0.537, 95% CI = 0.323-0.894, and = 0.017). Our findings suggested that the (R)-CDOP regimen had a lower risk of cardiovascular adverse events in non-Hodgkin's lymphoma than the (R)-CHOP regimen, demonstrating its safety with regard to cardiotoxicity. In addition, this study found the (R)-CDOP regimen was no less efficacious than the (R)-CHOP regimen in the treatment of non-Hodgkin's lymphoma. These findings need to be validated by higher-quality research because of the limited number and quality of included studies.
PubMed: 36532720
DOI: 10.3389/fphar.2022.1060668 -
Clinical Oral Investigations Jan 2023To investigate the association between asthma and oral conditions in children and adolescents. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To investigate the association between asthma and oral conditions in children and adolescents.
MATERIAL AND METHODS
Observational studies that evaluated the association between asthma and oral conditions in children and/or adolescents were retrieved from five databases, grey literature and reference lists up to April 7, 2022. Meta-analyses were performed, and I statistics were calculated. The mean difference was used as a measure of effect for continuous variables. Event frequencies were evaluated to determine odds ratios for dichotomous variables. Publication bias was investigated using Egger's test. The methodological quality (JBI) and certainty of the evidence (GRADE) were assessed.
RESULTS
Forty-two studies were eligible, and sixteen were included in the meta-analysis. Mean dmft (MD: 1.11, 95%CI: 0.48-1.73), DMFT (MD: 1.01, 95% CI: 0.45-1.56), dmfs (MD: 3.62, 95%CI: 2.60-4.63) and DMFS (MD: 4.47, 95%CI: 0.98-7.96) indices were significantly higher in asthmatic children and adolescents compared to those without asthma. In the analysis of biofilm, asthmatic children and adolescents had a higher Plaque Index compared to those without asthma (MD: 0.18, 95%CI: 0.03-0.33).
CONCLUSION
Asthmatic children and adolescents may be more likely to develop tooth decay and build up biofilm compared to those without asthma. It is suggested that there are no differences between asthmatic and non-asthmatic children and adolescents regarding gingivitis, developmental defects of enamel or erosive tooth wear. The certainty of the evidence was classified as 'very low'.
CLINICAL RELEVANCE
Knowledge of the risks that asthma and asthma medications for oral health can assist in counselling families of children and adolescents with this condition in terms of control and prevention measures for oral problems.
Topics: Adolescent; Child; Humans; Dental Caries; Doxorubicin; Fluorouracil; Gingivitis; Oral Health; Asthma
PubMed: 36459238
DOI: 10.1007/s00784-022-04803-4 -
Frontiers in Pharmacology 2022The Platinum-based combination has been proven to have an outstanding effect on patients with platinum-sensitive recurrent ovarian cancer (PSROC), but the best...
The Platinum-based combination has been proven to have an outstanding effect on patients with platinum-sensitive recurrent ovarian cancer (PSROC), but the best scientific combination has not been established yet. The present study is aimed to seek the best treatment plan for PSROC. We did a systematic review and Bayesian network meta-analysis, during which lite before March 2022 were retrieved on PubMed, Embase, Web of Science, and Cochrane Central Registry of Controlled databases. We included randomized controlled clinical trials comparing chemotherapy combinations with other treatments for patients with PSROC. The important outcomes concerned were progression-free survival (PFS) (the primary outcome), overall survival (OS), objective response rate (ORR), adverse events (AEs), and AEs-related discontinuation. All outcomes were ranked according to the surface under the cumulative ranking curve. 26 trials involving 10441 patients were retrieved in this study. For the initial treatment of PSROC, carboplatin plus pegylated liposomal doxorubicin (PLD) plus bevacizumab had the best PFS [hazard ratio (HR) 0.59, 95% credible interval (CI) 0.51-0.68]; Carboplatin plus paclitaxel plus bevacizumab resulted in the best OS (HR 1.22, 95% CI 1.09-1.35) and ORR [odds ratio (OR) 1.22, 95% CI 1.09-1.35]. For the maintenance therapy in PSROC, poly (ADP-ribose) polymerase inhibitors (PARPi) following platinum-based chemotherapy provided the best PFS (HR 0.64, 95% CI 0.61-0.68), the highest frequency of adverse events of grade three or higher (OR 0.18, 95% CI 0.07-0.44) but the treatment discontinuation was generally low. Subgroup analysis suggested that trabectedin plus PLD was comparable to single platinum in prolonging PFS in the platinum-free interval (6-12 months). Both platinum-based chemotherapy plus PARPi and platinum-based chemotherapy plus bevacizumab had higher survival benefits than other treatments in PSROC. Trabectedin plus PLD might be a potential alternative treatment strategy for the partially platinum-sensitive subpopulation with intolerance to platinum. : [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42022326573].
PubMed: 36438821
DOI: 10.3389/fphar.2022.1010626 -
Oncogene Jan 2023Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate,...
Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Clinical Relevance; Doxorubicin; Neoplasm Recurrence, Local; Osteosarcoma; Drug Resistance, Neoplasm
PubMed: 36434179
DOI: 10.1038/s41388-022-02529-x -
Frontiers in Oncology 2022The main objective of this systematic review was to examine the literature evaluating association of image-based body composition with chemotherapy-related toxicity in...
OBJECTIVES
The main objective of this systematic review was to examine the literature evaluating association of image-based body composition with chemotherapy-related toxicity in ovarian cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across studies.
METHODS
This systematic review was conducted according to the PRISMA-DTA statement and the protocol was registered on Prospero. A comprehensive literature search of 3 electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study data; population characteristics; technical aspects; body composition features; chemotherapy drugs administered; association of body composition values and toxicities. The overall quality of the included studies was critically evaluated.
RESULTS
After the initial retrieval of 812 articles, the systematic review included 6 articles (5/6 studies were retrospective; one was prospective). The number of patients ranged between 69 and 239; mean/median age ranged between 55 and 65 years; the percentage of sarcopenic patients ranged between 25% and 54%. The cut-off values to define sarcopenia and the vertebral levels for evaluation of body composition were different. Five studies included chemotherapy based on carboplatin and paclitaxel, 1 included chemotherapy based on pegylated liposomal doxorubicin. Among the studies including carboplatin and paclitaxel, 3/5 demonstrated an association with toxicity, whereas 2/5 did not. Altogether, 4/6 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities.
CONCLUSIONS
There is a wide variability of results about the association of body composition and chemotherapy-related toxicity in ovarian cancer patients. Therefore further studies, possibly including a comprehensive assessment of body compartments and where the definition of body composition cut-offs is constant, are warranted to better understand this association.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier (CRD42022337753).
PubMed: 36408182
DOI: 10.3389/fonc.2022.1057631 -
Frontiers in Oncology 2022The ecteinascidins trabectedin and lurbinectedin are very interesting antineoplastic agents, with a favorable toxicity profile and peculiar mechanisms of action. These...
Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma.
The ecteinascidins trabectedin and lurbinectedin are very interesting antineoplastic agents, with a favorable toxicity profile and peculiar mechanisms of action. These drugs form adducts in the minor groove of DNA, which produce single-strand breaks (SSBs) and double-strand breaks (DSBs) and trigger a series of events resulting in cell cycle arrest and apoptosis. Moreover, the ecteinascidins interact with the tumor microenvironment, reduce the number of tumor-associated macrophages, and inhibit the secretion of cytokines and chemokines. Trabectedin has been approved by the Federal Drug Administration (FDA) for patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-based regimen. Moreover, trabectedin in combination with pegylated liposomal doxorubicin (PLD) has been approved in the European Union for the treatment of platinum-sensitive recurrent ovarian cancer. Lurbinectedin has been approved by the FDA for patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. The review assesses and experimental studies on the antineoplastic effects of both ecteinascidins as well as the clinical trials on the activity of trabectedin in uterine sarcoma and ovarian carcinoma and of lurbinectedin in ovarian carcinoma and endometrial carcinoma.
PubMed: 36408147
DOI: 10.3389/fonc.2022.914342 -
Clinical Genitourinary Cancer Feb 2023Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare... (Review)
Review
A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.
Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Cisplatin; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36376169
DOI: 10.1016/j.clgc.2022.10.011