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Blood Reviews Nov 2016Most knowledge of hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) is derived from pediatric studies; literature on adult HPS/HLH... (Meta-Analysis)
Meta-Analysis Review
Most knowledge of hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) is derived from pediatric studies; literature on adult HPS/HLH predominantly consists of small retrospective studies with clinical and methodological heterogeneity. The aims of this systematic scoping review were to provide an overview of existing literature on adult HPS/HLH, describe current practices in diagnosis and treatment, and propose priorities for future research. Articles from Ovid Medline, Embase and Pubmed (1975-2015) describing 10 or more unique adults (age>15years) with HPS/HLH were included. 82 publications were eligible: 10 were prospective and 72 were retrospective. Of the six distinct diagnostic criteria, the HLH-2004 criteria were by far the most commonly used. A minority of studies tested for genetic abnormalities (12), soluble interleukin-2 receptor (11), and/or NK function (11) in a subset of patients. Most centers used steroids and either etoposide-based (HLH-94/HLH-2004) or doxorubicin-based (CHOP) initial therapy regimens. Allogeneic hematopoietic cell therapy for treatment of adult HLH has rarely been reported. Mortality in larger treatment focused studies ranged from 20 to 88%. Developing adult-specific diagnostic criteria based on widely evaluable features of secondary HPS/HLH and establishing standard initial therapies are priorities for future research.
Topics: Combined Modality Therapy; Disease Susceptibility; Humans; Lymphohistiocytosis, Hemophagocytic; Practice Guidelines as Topic; Prognosis; Treatment Outcome
PubMed: 27238576
DOI: 10.1016/j.blre.2016.05.001 -
The Oncologist Jun 2016Platinum-based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle-invasive bladder cancer patients. We performed a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Platinum-based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle-invasive bladder cancer patients. We performed a systematic review and meta-analysis to provide updated results of previous findings. We also summarized published data to compare clinical outcomes of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) versus gemcitabine and cisplatin/carboplatin (GC) in the neoadjuvant setting.
METHODS
A meta-analysis of 15 randomized clinical trials was performed to compare neoadjuvant chemotherapy plus local treatment with the same local treatment alone. Because no randomized trials have investigated MVAC versus GC in the neoadjuvant setting, a meta-analysis of 13 retrospective studies was performed to compare MVAC with GC.
RESULTS
A total of 3,285 patients were included in 15 randomized clinical trials. There was a significant overall survival (OS) benefit associated with cisplatin-based neoadjuvant chemotherapy (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96). A total of 1,766 patients were included in 13 retrospective studies. There was no significant difference in pathological complete response between MVAC and GC. However, GC was associated with a significantly reduced overall survival (HR, 1.26; 95% CI, 1.01-1.57). After excluding carboplatin data, GC still seemed to be inferior to MVAC in OS (HR, 1.31; 95% CI, 0.99-1.74), but the difference was no longer statistically significant.
CONCLUSION
These results support the use of cisplatin-based combination neoadjuvant chemotherapy in muscle-invasive bladder cancer. Although GC and MVAC had similar treatment response rates, the different survival outcome observed in this study requires further investigation.
IMPLICATIONS FOR PRACTICE
Platinum-based neoadjuvant chemotherapy (NCT) has been shown to improve survival outcomes in muscle-invasive bladder cancer (MIBC) patients, but the optimal neoadjuvant regimen has not been established. Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin/carboplatin (GC) are two of the most commonly used chemotherapy regimens in modern oncology. In this two-step meta-analysis, an updated and more precise estimate of the survival benefit of cisplatin-based NCT in MIBC is provided. This study also demonstrated that MVAC might have superior overall survival compared with GC (with or without carboplatin data) in the neoadjuvant setting. The findings suggest that NCT should be standard care in MIBC, and MVAC could be the preferred neoadjuvant regimen.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Humans; Neoadjuvant Therapy; Neoplasm Invasiveness; Urinary Bladder Neoplasms
PubMed: 27053504
DOI: 10.1634/theoncologist.2015-0440 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
Frontiers in Pharmacology 2023Doxorubicin-induced cardiotoxicity represents a prevalent adverse effect encountered in patients undergoing treatment with doxorubicin. To date, there has been no...
Doxorubicin-induced cardiotoxicity represents a prevalent adverse effect encountered in patients undergoing treatment with doxorubicin. To date, there has been no bibliometric study to summarize the field of doxorubicin-induced cardiotoxicity. In our study, we aim to determine the current status and frontiers of doxorubicin-induced cardiotoxicity by bibliometric analysis. The documents concerning doxorubicin-induced cardiotoxicity are obtained from the Web of Science Core Collection database (WOSCC), and VOSviewer 1.6.16, CiteSpace 5.1.3 and the WOSCC's literature analysis wire were used to conduct the bibliometric analysis. In total, 7,021 publications were encompassed, which are produced by 37,152 authors and 6,659 organizations, 1,323 journals, and 101 countries/regions. The most productive author, institution, country and journal were Bonnie Ky with 35 publications, University of Texas with 190 documents, the United States with 1,912 publications, and with 120 documents. The first high-cited article was published in the NEJM with 8,134 citations authored by DJ Slamon et al., in 2001. For keyword analysis, there are four clusters depicted in distinct directions. The keywords in the red cluster are oxidative stress, apoptosis, and cardiomyopathy. The keywords in the green cluster are cardiotoxicity, heart failure, and anthracycline. The keywords in the blue cluster are chemotherapy, trastuzumab, and paclitaxel. The keywords in the purple cluster are doxorubicin, adriamycin, and cancer. Most of the documents were derived from the United States, China and Italy (4,080/7,021, 58.1%). The number of studies from other countries should be increased. In conclusion, the main research hotspots and frontiers in the field of doxorubicin-induced cardiotoxicity include the role of doxorubicin in cardiotoxicity, the mechanisms underlying doxorubicin-induced cardiotoxicity, and the development of treatment strategies for doxorubicin-induced cardiotoxicity. More studies are needed to explore the mechanisms and treatment of doxorubicin-induced cardiotoxicity.
PubMed: 38026961
DOI: 10.3389/fphar.2023.1255158 -
Cancer Aug 2008The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival.
METHODS
A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model.
RESULTS
Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy.
CONCLUSIONS
This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.
Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Odds Ratio; Randomized Controlled Trials as Topic; Sarcoma; Survival Analysis
PubMed: 18521899
DOI: 10.1002/cncr.23592 -
Health Technology Assessment... Jan 2015Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line... (Comparative Study)
Comparative Study Meta-Analysis Review
Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation.
BACKGROUND
Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer.
OBJECTIVES
To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer.
DATA SOURCES
Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013.
METHODS
A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed.
RESULTS
For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated.
LIMITATIONS
As platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease.
CONCLUSIONS
For platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013003555.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Deoxycytidine; Dioxoles; Disease-Free Survival; Double-Blind Method; Doxorubicin; Female; Health Care Costs; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Tetrahydroisoquinolines; Topotecan; Trabectedin; Treatment Outcome; United Kingdom; Gemcitabine
PubMed: 25626481
DOI: 10.3310/hta19070 -
Translational Oncology Jul 2024Doxorubicin (DOX) a chemotherapy drug often leads to the development of resistance, in cancer cells after prolonged treatment. Recent studies have suggested that using... (Review)
Review
INTRODUCTION
Doxorubicin (DOX) a chemotherapy drug often leads to the development of resistance, in cancer cells after prolonged treatment. Recent studies have suggested that using metformin plus doxorubicin could result in synergic effects. This study focuses on exploring the co-treat treatment of doxorubicin and metformin for various cancers.
METHOD
Following the PRISMA guidelines we conducted a literature search using different databases such as Embase, Scopus, Web of Sciences, PubMed, Science Direct and Google Scholar until July 2023. We selected search terms based on the objectives of this study. After screening a total of 30 articles were included.
RESULTS
The combination of doxorubicin and metformin demonstrated robust anticancer effects, surpassing the outcomes of monotherapy drug treatment. In vitro experiments consistently demonstrated inhibition of cancer cell growth and increased rates of cell death. Animal studies confirmed substantial reductions in tumor growth and improved survival rates, emphasizing the synergistic impact of the combined therapy. The research' discoveries collectively emphasize the capability of the co-treat doxorubicin-metformin as a compelling approach in cancer treatment, highlighting its potential to address medicate resistance and upgrade generally helpful results.
CONCLUSION
The findings of this study show that the combined treatment regimen including doxorubicin and metformin has significant promise in fighting cancer. The observed synergistic effects suggest that this combination therapy could be valuable, in a setting. This study highlights the need for clinical research to validate and enhance the application of the doxorubicin metformin regimen.
PubMed: 38636389
DOI: 10.1016/j.tranon.2024.101946 -
Annals of Translational Medicine Dec 2021This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).
BACKGROUND
This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).
METHODS
Multiple databases, including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure, were searched to retrieve relevant articles. Ultimately, the full text of 10 studies involving the use of trabectedin and doxorubicin in STS were reviewed. Review Manager 5.2 was used to evaluate the heterogeneity of the results of the selected articles. Forest plot, bias, and sensitivity analyses were carried out on the included articles.
RESULTS
Ten papers that met the criteria were included in this analysis. STS patients receiving trabectedin had longer progression-free survival than those receiving doxorubicin [overall mean difference (MD) =1.36, 95% confidence interval (CI): 1.04, 1.68, I=6%, fixed-effects model]. The experimental group also had a longer overall survival period than the control group (MD =3.92, 95% CI: 0.23, 7.60, P=0.04 and I=83%, random-effects model), and the experimental group had a better disease control rate than the control group (relative risk =1.2, P=0.03 and I=45%, fixed-effects model). From the publication bias analysis and sensitivity analysis, we can guarantee the results are robust and unbiased.
DISCUSSION
Our research showed that STS patients who received trabectedin had better clinical effects and a longer survival time than those who received doxorubicin.
PubMed: 35071458
DOI: 10.21037/atm-21-6033 -
Journal of Oncology 2022This study aimed to review the potential chemoprotective effects of curcumin against the doxorubicin-induced cardiotoxicity. (Review)
Review
OBJECTIVE
This study aimed to review the potential chemoprotective effects of curcumin against the doxorubicin-induced cardiotoxicity.
METHODS
According to the PRISMA guideline, a comprehensive systematic search was performed in different electronic databases (Web of Science, PubMed, and Scopus) up to July 2021. One hundred and sixty-four studies were screened in accordance with a predefined set of inclusion and exclusion criteria. Eighteen eligible articles were finally included in the current systematic review.
RESULTS
According to the in vitro and in vivo findings, it was found that doxorubicin administration leads to decreased cell survival, increased mortality, decreased bodyweight, heart weight, and heart to the bodyweight ratio compared to the control groups. However, curcumin cotreatment demonstrated an opposite pattern in comparison with the doxorubicin-treated groups alone. Other findings showed that doxorubicin significantly induces biochemical changes in the cardiac cells/tissue. Furthermore, the histological changes on the cardiac tissue were observed following doxorubicin treatment. Nevertheless, for most of the cases, these biochemical and histological changes mediated by doxorubicin were reversed near to control groups following curcumin coadministration.
CONCLUSION
It can be mentioned that coadministration of curcumin alleviates the doxorubicin-induced cardiotoxicity. Curcumin exerts these cardioprotective effects through different mechanisms of antioxidant, antiapoptosis, and anti-inflammatory. Since the finding presented in this systematic review are based on in vitro and in vivo studies, suggesting the use of curcumin in cancer patients as a cardioprotector agent against cardiotoxicity mediated by doxorubicin requires further clinical studies.
PubMed: 35237323
DOI: 10.1155/2022/7277562 -
Frontiers in Cardiovascular Medicine 2023Recently, attention has been paid to the protective properties of active ingredients in (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the... (Review)
Review
BACKGROUND
Recently, attention has been paid to the protective properties of active ingredients in (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on models of doxorubicin-induced cardiotoxicity (DIC).
METHODS
According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant studies on "the role of AISM on DIC" published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias.
RESULTS
Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, . The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool.
CONCLUSION
This systematic review demonstrated that AISM have chemoprotective effects on DIC and models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.
PubMed: 37915739
DOI: 10.3389/fcvm.2023.1267525