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The Cochrane Database of Systematic... Jan 2009Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal... (Review)
Review
BACKGROUND
Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management.
OBJECTIVES
To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM).
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.
MAIN RESULTS
One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia.
AUTHORS' CONCLUSIONS
Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This review demonstrated that there is currently no evidence to suggest that alkylating agents are effective in treating Waldenstrom's macroglobulinaemia.
Topics: Alkylating Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Prednisone; Randomized Controlled Trials as Topic; Vidarabine; Waldenstrom Macroglobulinemia
PubMed: 19160296
DOI: 10.1002/14651858.CD006719.pub3 -
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 -
Current Drug Metabolism 2018Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of... (Review)
Review
BACKGROUND
Anthracyclines in combination with cytarabine have been the standard therapy for acute myeloid leukemia (AML) for decades with high efficacy. However, the majority of patients will show initial resistance or will relapse after initial complete remission. Genetic variability in genes involved in anthracyclines metabolic pathway could be one of the causes of the interindividual differences in clinical outcomes.
METHODS
A systematic review of published studies in AML cohorts was carried out in order to analyze the influence of polymorphisms in genes of anthracycline metabolism on efficacy and toxicity.
RESULTS
Polymorphisms in the main enzymes of anthracyclines metabolism (CBR, AKR, NQO1, NOS3) have been related to lower enzymatic activity and higher cardiotoxicity. Moreover, variant alleles in the genes of carcinogens and chemotherapy neutralizing enzymes (GST, SULT, NADP(H) oxidase) have been associated with ROS generation and drug efficacy, influencing the survival rates and cardiac toxicities. In addition, genetic variability in the transporters of anthracyclines could affect the intake in cells, including influx (SLC28A3, SLC22A12, SLCO1B1) and efflux transporters (ABCB1, ABCC1, ABCC3, ABCG2).
CONCLUSION
The knowledge of the role of pharmacogenetics in anthracyclines metabolism could explain the differences observed in their disposition in leukemic cells. These genetic variants are proposed biomarkers in clinical practice in order to individualize chemotherapy schemes, potentially increasing the effectiveness and reducing the toxicities.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Humans; Leukemia, Myeloid, Acute; Pharmacogenetics; Polymorphism, Genetic
PubMed: 29090664
DOI: 10.2174/1389200218666171101124931 -
Cancer Treatment Reviews Feb 2018Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.
METHODS
We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.
RESULTS
We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053).
CONCLUSION
Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Sarcoma
PubMed: 29253836
DOI: 10.1016/j.ctrv.2017.12.003 -
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 -
The Lancet. Oncology Oct 2011No standard monotherapy or combination palliative chemotherapy currently exists for patients with advanced breast cancer pretreated with anthracyclines and taxanes. In... (Review)
Review
No standard monotherapy or combination palliative chemotherapy currently exists for patients with advanced breast cancer pretreated with anthracyclines and taxanes. In this systematic review we assess the current knowledge on the efficacy and safety of palliative single-agent chemotherapy drugs--capecitabine, vinorelbine, gemcitabine, and liposomal doxorubicin--commonly used in daily clinical practice. We identified 22 studies, of which ten investigated capecitabine, nine investigated vinorelbine, three investigated gemcitabine, and one investigated liposomal doxorubicin. The greatest amount of information was available for capecitabine and vinorelbine. These two drugs showed good efficacy. The disease control rate differed significantly between the four drugs, which is relevant in terms of how well tumour symptoms can be improved and whether quality of life can be maintained or even improved. To obtain more evidence of the efficacy and safety of chemotherapeutic agents used in this pretreated population of advanced breast cancer patients, randomised comparisons of the various drugs, as monotherapy and in combination with targeted agents, are needed.
Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Deoxycytidine; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Middle Aged; Palliative Care; Quality of Life; Risk Assessment; Survival Rate; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine; Gemcitabine
PubMed: 21621462
DOI: 10.1016/S1470-2045(11)70045-6 -
Health Technology Assessment... 2002
Review
Topics: Aged; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Middle Aged; Outcome Assessment, Health Care; Ovarian Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; State Medicine; Survival; United Kingdom
PubMed: 12433314
DOI: 10.3310/hta6230 -
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 -
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 -
Acta Oncologica (Stockholm, Sweden) 2016R-CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma. It was suggested that decreasing the treatment interval from three weeks... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
R-CHOP-21 has remained the standard chemotherapy for aggressive non-Hodgkin's lymphoma. It was suggested that decreasing the treatment interval from three weeks (CHOP-21) to two weeks (CHOP-14) may improve survival and disease control of patients with aggressive lymphoma.
PURPOSE
To evaluate the effect of CHOP-like-14 (with or without rituximab) compared to standard CHOP-like -21 on overall survival (OS), disease control and toxicity of patients with aggressive non-Hodgkin lymphoma.
METHODS
Systematic review and meta-analysis of RCTs. In October 2014 we searched The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Authors were contacted for complementary data. The primary outcome was OS.
RESULTS
We identified seven trials (4073 patients), conducted between the years 1999 and 2008. Trials were at low or unclear risk for selection bias, and at low or unclear risk of attrition bias. CHOP-like-14 improved OS of patients with aggressive lymphoma compared to the same regimen given every 21 days (all trials): HR of death 0.86, 95% confidence interval (CI) 0.77-0.97. There was no OS difference between rituximab-CHOP-like 14 to rituximab-CHOP-like-21 (3 trials): HR 0.93 95% CI 0.78-1.10. The rates of progression or death, complete response, treatment-related mortality, grade 3-4 infection, and discontinuation were similar between groups.
CONCLUSION
R-CHOP-21 remains the standard of care for patient with aggressive B-cell lymphoma. CHOP-14 can be considered as in case rituximab is omitted.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Prednisone; Randomized Controlled Trials as Topic; Rituximab; Vincristine
PubMed: 25997705
DOI: 10.3109/0284186X.2015.1043025