-
Clinical Lymphoma, Myeloma & Leukemia Dec 2018The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin.
PATIENTS AND METHODS
The present systematic review and meta-analysis compared the efficacy and toxicity between IDA and high-dose daunorubicin (HDD) for induction therapy for adult AML. Relevant studies reported before June 2018 were searched from the Medline and Embase databases.
RESULTS
A total of 5 studies with 1809 participants (3 randomized controlled studies and 2 retrospective cohort studies) met the eligibility criteria and were included in the meta-analysis. The patients in the IDA arm for induction therapy had a significantly greater complete response rate after the first course of induction therapy compared with those in the HDD arm (66.7% vs. 61.1%, respectively; odds ratio, 1.23; P = .04; I = 0%). A significantly lower rate of refractory AML was also observed in the IDA group than in the HDD group (16.8% vs. 20.7%, respectively; odds ratio, 0.77; P = .04; I = 0%). However, no difference was found in the long-term overall survival between the 2 groups. Also, the induction mortality rate, febrile neutropenia rate, and cardiotoxicity rate were not significantly different between the 2 groups. The major limitation was the relatively small number of included studies, which could have limited the power of the meta-analysis to demonstrate significant long-term benefits.
CONCLUSION
The complete response rate after the first course of induction therapy was significantly greater among adult patients with AML who had received IDA as part of induction therapy compared with those who had received HDD.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Daunorubicin; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Odds Ratio; Remission Induction; Treatment Outcome; Young Adult
PubMed: 30241991
DOI: 10.1016/j.clml.2018.08.008 -
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 -
PloS One 2024Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems... (Meta-Analysis)
Meta-Analysis
Comparison of neoadjuvant treatment and surgery first for resectable or borderline resectable pancreatic carcinoma: A systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Current treatment recommendations for resectable or borderline pancreatic carcinoma support upfront surgery and adjuvant therapy. However, neoadjuvant therapy (NT) seems to increase prognosis of pancreatic carcinoma and come to everyone's attention gradually. Randomized controlled trials offering comparison with the NT are lacking and optimal neoadjuvant treatment regimen still remains uncertain. This study aims to compare both treatment strategies for resectable or borderline resectable pancreatic cancer.
METHODS
The PRISMA checklist was used as a guide to systematically review relevant peer-reviewed literature reporting primary data analysis. We searched PubMed, Medline, EMBASE, Cochrane Datebase and related reviews for randomized controlled trials comparing neoadjuvant therapy with surgery first for resectable or borderline resectable pancreatic carcinoma. We estimated relative hazard ratios (HRs) for median overall survival and ratios risks (RRs) for microscopically complete (R0) resection among different neoadjuvant regimens and major complications. We assessed the effects of neoadjuvant therapy on R0 resection rate and median overall survival with Bayesian analysis.
RESULTS
Thirteen eligible articles were included. Eight studies performed comparison neoadjuvant therapy with surgery first, and R0 resection rate was recorded in seven studies. Compared with surgery first, neoadjuvant therapy did increase the R0 resection rate (RR = 1.53, I2 = 0%, P< 0.00001), there was a certain possibility that gemcitabine + cisplatin (Gem+Cis) + Radiotherapy was the most favorable in terms of the fact that there was no significant difference concerning the results from the individual studies. In direct comparison, four studies were included and estimated that Neoadjuvant therapy improved mOS compared with upfront surgery (HR 0.68, 95% CI 0.58-0.92; P = 0.012; I2 = 15%), after Bayesian analysis it seemed that regimen with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) was most likely the best with a relatively small sample size. The rate of major surgical complications was available for six studies and ranged from 11% to 56% with neoadjuvant therapy and 11% to 45% with surgery first. There was no significant difference between neoadjuvant therapy and surgery first, also with a high heterogeneity (RR = 0.96, 95%CI = 0.65-1.43; P = 0.85; I2 = 46%).
CONCLUSION
In conclusion neoadjuvant therapy might offer benefit over up-front surgery. Neoadjuvant therapy increased the R0 resection rate with gemcitabine + cisplatin + Radiotherapy that was the most favorable and improved mOS with Cisplatin/ Epirubicin then Gemcitabine/ Capecitabine (PEXG) that was most likely the best.
Topics: Humans; Neoadjuvant Therapy; Gemcitabine; Capecitabine; Cisplatin; Epirubicin; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic; Pancreatic Neoplasms; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38451955
DOI: 10.1371/journal.pone.0295983 -
Critical Reviews in Oncology/hematology Nov 2021CNS prophylaxis is commonly used in Diffuse Large B-Cell Lymphoma (DLBCL) patients with risk features for CNS relapse. This systematic review and meta-analysis compares... (Meta-Analysis)
Meta-Analysis Review
CNS prophylaxis is commonly used in Diffuse Large B-Cell Lymphoma (DLBCL) patients with risk features for CNS relapse. This systematic review and meta-analysis compares CNS relapse rates with and without CNS prophylaxis, for patients at intermediate to high CNS relapse risk. Studies reporting CNS relapse risk category and CNS outcomes with and without CNS prophylaxis for antiCD20-CHOP treated DLBCL patients were included. 10 studies with 3770 patients at intermediate to high CNS relapse risk were analyzed. No significant difference in the pooled Absolute Risk Difference (ARD 0.01, 95 % CI -0.01 to 0.02, P = 0.61) or Risk (RR 1.22, 95 % CI 0.81-1.83, P = 0.34) was noted in patients with and without CNS prophylaxis. There were also no differences within pre-specified subgroups of IV Methotrexate or IT chemotherapy. However, the quality of evidence supporting these observations was low. A meta-analysis of individual patient data will help evaluate the benefit of CNS prophylaxis strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Rituximab; Vincristine
PubMed: 34656744
DOI: 10.1016/j.critrevonc.2021.103507 -
Critical Reviews in Oncology/hematology Oct 2016This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in... (Meta-Analysis)
Meta-Analysis Review
This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Fluorodeoxyglucose F18; Humans; Lymphoma, Large B-Cell, Diffuse; Positron-Emission Tomography; Prednisone; Radiopharmaceuticals; Rituximab; Tomography, X-Ray Computed; Vincristine
PubMed: 27637352
DOI: 10.1016/j.critrevonc.2016.07.003 -
The Oncologist Dec 2017Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded.
MATERIAL AND METHODS
PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS. Two independent investigators extracted data; the quality of eligible studies was resolved by consensus. Hazard ratio (HR) of death and progression (OS and progression-free survival [PFS]) and odds ratio (OR) for response rate (RR) were pooled in a fixed- or random-effects model according to heterogeneity. Study quality was assessed with the Cochrane's risk of bias tool, and publication bias with funnel plots.
RESULTS
Overall, 10 randomized trials were selected. The pooled HR for death was 0.81 (95% confidence interval [CI] 0.73-0.9). Second-line therapy reduced the risk of progression by 49% (HR = 0.51, 95% CI 0.34-0.76). This translated into an absolute benefit in OS and PFS by 3.3 and 1.6 months, respectively. Finally, RR with new agents or chemotherapy doublets translated from 4.3% to 7.6% (OR = 1.78, 95% CI 1.22-2.50).
CONCLUSION
Better survival is achieved in patients treated with salvage therapies (chemotherapy, as single or multiple agents or targeted biological agents). A 3-months gain in OS and an almost double RR is observed. Second lines also attained a reduction by 50% the risk of progression.
IMPLICATIONS FOR PRACTICE
There is some evidence that salvage therapies after first-line failure are able to improve outcome in metastatic soft tissue sarcoma (STS). Trabectedin, gemcitabine-based therapy, and pazopanib are currently approved drugs used after conventional upfront treatment. This meta-analysis reviews the benefit of new agents used in randomized trials in comparison with no active treatments or older agents for recurrent/progressed STS. The results show that modern drugs confer a statistically significant 3-month benefit in terms of overall survival, and an increase in response rate. Despite a limited improvement in outcome, currently approved second-line therapy should be offered to patients with good performance status.
Topics: Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Salvage Therapy; Sarcoma
PubMed: 28835514
DOI: 10.1634/theoncologist.2016-0474 -
Critical Reviews in Oncology/hematology Apr 2021Diffuse large B cell Lymphoma (DLBCL) is a potentially curative lymphoma with increasing incidence with ageing. Treatment of elderly DLBCL patients represents a... (Review)
Review
INTRODUCTION
Diffuse large B cell Lymphoma (DLBCL) is a potentially curative lymphoma with increasing incidence with ageing. Treatment of elderly DLBCL patients represents a particular challenge due to their comorbidities and performance status.
METHODS
A search for original articles focused on the treatment of elderly DLBCL patients was performed in PubMed database and 633 were found and reviewed. Thirty-eight studies meeting our inclusion criteria were published since 2007.
RESULTS
Thirteen studies were retrospective and 25 phase II/III clinical trials. Most of them investigated the efficacy of dose-adjusted R-CHOP regimen. Alternative therapeutic drugs together with geriatric assessment were also evaluated. For fit patients aged 80 and over, the strongest evidence favours R-miniCHOP regimen.
CONCLUSION
A dose-adjusted R-CHOP may be the recommended treatment in elderly DLBCL patients. New tools such as the Comprehensive Geriatric Assessment provide useful guidance for treatment choice, based on comorbidities and frailty index of this group.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Comorbidity; Cyclophosphamide; Doxorubicin; Geriatric Assessment; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Retrospective Studies; Rituximab; Treatment Outcome; Vincristine
PubMed: 33675907
DOI: 10.1016/j.critrevonc.2021.103294 -
European Journal of Cancer (Oxford,... Nov 2015Anthracyclines play a broad and important role in the care of patients with either operable or metastatic breast cancer. However cardiotoxicity narrows the therapeutic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anthracyclines play a broad and important role in the care of patients with either operable or metastatic breast cancer. However cardiotoxicity narrows the therapeutic index of this drug class leading to potentially clinically meaningful treatment delays or discontinuations. We conducted a Bayesian network meta-analysis, a validated statistical methodology, allowing direct and indirect comparison of cardiotoxicity of different anthracycline and non-anthracycline regimens.
METHODS
We conducted a systematic review of prospective randomised controlled trials through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Google Scholar comparing non-anthracycline based regimens (NON), doxorubicin (DOX), epirubicin (EPI) and liposomal doxorubicin (LD). We included studies published up to 1st January 2014 in both adjuvant and metastatic contexts. Notably, HER2/neu-targeted regimens were excluded. We assessed the studies' eligibility criteria and data collection with consensus of two independent authors. Our primary outcome measure was cardiac events grade 3 or greater (CE3) in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. A Bayesian pairwise and network meta-analysis was conducted to estimate pooled Odds Ratio (OR).
FINDINGS
Nineteen randomised controlled trials met eligibility criteria and were included in this analysis. We found a trend showing that LD is less cardiotoxic than DOX with an OR of 0.60 (95% confidence interval (CI) 0.34-1.07) There was no difference between Epi and LD with an OR of 0.95 (95%CI 0.39-2.33). DOX is more cardiotoxic than Non with an OR of 1.57 (95%CI 0.90-2.72).
INTERPRETATION
DOX has higher CE3 rates than NON does. LD statistically trended to lower cardiac event rates than DOX. Non-statistical significance among EPI, LD and DOX with regard to cardiac toxicity indicates that avoidance of CE3 should not motivate selection of a particular anthracycline in otherwise healthy women in whom total lifetime anthracycline exposure will likely be limited. Overall low incidence of CE3 with any type of anthracycline indicates that we can safely use any anthracycline if cumulative dose limits are not exceeded. While CE3 does not limit our choice of anthracycline LD appears to be the least cardiotoxic.
FUNDING
Takeo Fujii is supported by the grant named Young Investigator Award for Study Abroad in Clinical Epidemiology from St. Luke's Life Science Institution.
Topics: Antibiotics, Antineoplastic; Bayes Theorem; Breast Neoplasms; Doxorubicin; Epirubicin; Female; Heart Diseases; Humans; Odds Ratio; Patient Selection; Polyethylene Glycols; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors
PubMed: 26343314
DOI: 10.1016/j.ejca.2015.07.031 -
Musculoskeletal Surgery Mar 2023Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered... (Review)
Review
Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.
Topics: Humans; Vinorelbine; Sorafenib; Imatinib Mesylate; Hydroxyurea; Fibromatosis, Aggressive; Watchful Waiting; Methotrexate; Doxorubicin
PubMed: 35150408
DOI: 10.1007/s12306-022-00738-x