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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 -
The Cochrane Database of Systematic... Aug 2014Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES
To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA
Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS
We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS
The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.
Topics: Alitretinoin; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Bleomycin; Doxorubicin; Drug Therapy, Combination; Etoposide; HIV Infections; Humans; Liposomes; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sarcoma, Kaposi; Skin Neoplasms; Tretinoin; Vincristine
PubMed: 25221796
DOI: 10.1002/14651858.CD003256.pub2 -
Expert Opinion on Drug Metabolism &... Sep 2018BSTRACT Introduction: The aim of this study was to investigate the potential role of melatonin in the prevention of chemotherapy-induced nephrotoxicity at the... (Review)
Review
BSTRACT Introduction: The aim of this study was to investigate the potential role of melatonin in the prevention of chemotherapy-induced nephrotoxicity at the preclinical level. Areas to be covered: To illuminate the possible role of melatonin in preventing chemotherapy-related nephrotoxicity, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. A comprehensive search strategy was developed to include PubMed, Web of Science, Scopus, and Embase electronic databases from their inception to May 2018. Based on a set of prespecified inclusion and exclusion criteria, 21 non-clinical articles were ultimately included in the study. Expert opinion: Our findings clearly demonstrate that melatonin has a protective role in the prevention of chemotherapy-induced nephrotoxicity which may be caused by different chemotherapy agents such as cyclophosphamide, cisplatin, doxorubicin, methotrexate, oxaliplatin, etoposide, and daunorubicin. On the basis of current review of non-clinical studies, this protective effect of melatonin is attributed to different mechanisms such as reduction of oxidative stress, apoptosis, and inflammation. The findings presented in this review are based on non-clinical studies and thus conducting appropriate clinical trials to evaluate the real effectiveness of the concurrent use of chemotherapy agents with melatonin in the cancer patients is necessary.
Topics: Animals; Antineoplastic Agents; Apoptosis; Humans; Inflammation; Kidney Diseases; Melatonin; Neoplasms; Oxidative Stress
PubMed: 30118646
DOI: 10.1080/17425255.2018.1513492 -
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 -
Cardiology in Review 2018Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior studies have found conflicting results of whether nonstrain diastolic parameters can... (Meta-Analysis)
Meta-Analysis Review
Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior studies have found conflicting results of whether nonstrain diastolic parameters can predict doxorubicin-induced cardiotoxicity. We performed a systematic review of English written publications using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria were applied: cancer subjects, echo-derived nonstrain diastolic profile, and patients compared before and after treatment to predict systolic dysfunction. The following exclusion criteria were applied: other cardiotoxic agents, non-echo studies, or used protective medications. Meta-analysis was performed using comprehensive meta-analysis software V3 to calculate cumulative means, SD, and odds ratios (ORs). Only 4 studies were designed to predict doxorubicin-induced cardiotoxicity. Of the 7 common parameters identified among studies, only 4 were significant: mitral E [OR: 3.4; 95% confidence interval (CI): 1.5-7.8; P = 0.003]; lateral E' (OR: 3.7; 95% CI: 1.5-9.4; P < 0.005); mitral E/A (OR: 4.3; 95% CI: 2.1-8.9; P < 0.0001); and lateral S' (OR: 2.7; 95% CI: 1.2-5.8; P = 0.01). We found that conventional nonstrain diastolic parameters predicted doxorubicin-induced systolic dysfunction. Whether nonstrain diastolic parameters can be used to supplement strain imaging for predicting doxorubicin-induced systolic function warrants further investigation in larger studies.
Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Diastole; Doxorubicin; Echocardiography; Heart Ventricles; Humans; Neoplasms; Prognosis; Stroke Volume
PubMed: 29045286
DOI: 10.1097/CRD.0000000000000161 -
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 -
Expert Review of Clinical Pharmacology Mar 2019Induction chemotherapy based on anthracyclines and cytarabine (Ara-C) combination remains the standard of care for acute myeloid leukemia (AML) patients who are...
Induction chemotherapy based on anthracyclines and cytarabine (Ara-C) combination remains the standard of care for acute myeloid leukemia (AML) patients who are considered candidate for intensive and curative approaches. However, the toxicity of this regimen is high, with disappointing clinical outcomes among the so-called poor-prognosis AML subsets, which generally refer to patients with adverse cytogenetic risk, secondary AML including therapy-related AML, poor-prognosis mutations, especially FLT3-ITD, and relapse/refractory AML. Areas covered: To the best of our knowledge, the role and efficacy of 7 + 3 schedules containing daunorubicin (DNR) and Ara-C for certain types of poor-prognosis AML has not been systematically assessed. A critical approach to the role of DNR and Ara-C induction could be relevant to establish which patients should be enrolled in clinical trials using novel therapies. Expert commentary: In this regard, a recent randomized clinical trial (RCT) showed improved results in older patients with sAML or high-risk cytogenetics who received CPX-351 compared with standard 7 + 3 combination. We perform a systematic literature review to analyze the clinical outcomes reported with DNR plus Ara-C regimens in adult patients with poor-prognosis AML, the use of liposomal formulations of DNR and Ara-C and the RCTs which compared standard 7 + 3 with the addition of a third drug.
Topics: Adult; Animals; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Cytogenetic Analysis; Daunorubicin; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Mutation; Prognosis; Randomized Controlled Trials as Topic
PubMed: 30672340
DOI: 10.1080/17512433.2019.1573668 -
Critical Reviews in Oncology/hematology Jun 2016Docetaxel or Epirubicin-based regimens are both approved for the treatment of metastatic gastric cancer. We perform a systemic review with metanalysis to evaluate the... (Comparative Study)
Comparative Study Meta-Analysis Review
Docetaxel or Epirubicin-based regimens are both approved for the treatment of metastatic gastric cancer. We perform a systemic review with metanalysis to evaluate the efficacy and toxicities of docetaxel-based chemotherapy compared with epirubicin-containing regimens. A metaanalysis of randomized studies in accordance with the preference guidelines for reported items in systematic reviews and meta-analyses is performed in which the databases of PubMed, the Cochrane Library, and the ASCO University Meeting were searched for relevant publications. The primary outcome was efficacy, the secondary toxicities. A total of 553 cases were included in the meta-analysis; 278 received epirubicin-based treatment and 313 received docetaxel. The pooled risk ratio to achieve an objective response and a disease control rate were 1.08 (95% CI 0.85-1.37; P=0.52) and 0.90 (95% CI 0.75-1.08; P=0.27) respectively. EPI arm showed a decrease in the risk of neutropenia, anemia, fatigue, asthenia and diarrhea, paraesthesia; docetaxel arm showed a decrease in the risk of leucopenia, thrombocytopenia, anorexia, nausea, nausea-vomiting, stomatitis and neutropenic fever. The results of our study suggest a similar activity of docetaxel and epirubicin-based chemotherapeutic regimens in metastatic gastric cancer. Other parameters as, comorbidity, concomitant diseases and prior therapies should be taken into account to address the clinician's choice in selecting the best therapeutical approach for any single patient.
Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Epirubicin; Humans; Neoplasm Staging; Stomach Neoplasms; Taxoids; Treatment Outcome
PubMed: 27083592
DOI: 10.1016/j.critrevonc.2016.04.001 -
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