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Critical Reviews in Oncology/hematology Jun 2015Chronic lymphocytic leukemia (CLL) is a disease of the lymphoid system, in which the most common therapy is fludarabine plus cyclophosphamide (FC). The addition of... (Meta-Analysis)
Meta-Analysis Review
Rituximab, fludarabine, and cyclophosphamide versus fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia: A systematic review with meta-analysis.
BACKGROUND
Chronic lymphocytic leukemia (CLL) is a disease of the lymphoid system, in which the most common therapy is fludarabine plus cyclophosphamide (FC). The addition of rituximab to FC has been used, a combination known as FCR.
OBJECTIVES
To perform a systematic review with meta-analysis of clinical trials between 2000 and 2012 comparing FC and FCR in patients with CLL.
MATERIAL AND METHODS
Electronic databases were searched using keywords related to the objectives of this review. The outcomes examined were progression-free survival and complete remission.
RESULTS
The progression-free survival and the overall survival showed significant difference between the two regimens, with complete remission being more frequent in FCR-treated patients (odds ratio=2.58; 95% CI: 2.13-3.13). Patients treated with FCR showed significantly higher neutropenia and serious adverse reactions.
CONCLUSION
Despite the favorable results of the FCR regimen on outcomes including complete remission, progression-free survival, and overall survival, there is a lack of methodological rigor and appropriate analyses in many of these studies, and thus, there is a need for further studies examining the effect of rituximab in CLL patients.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Treatment Outcome; Vidarabine
PubMed: 25797826
DOI: 10.1016/j.critrevonc.2015.02.013 -
The Cochrane Database of Systematic... Oct 2016The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. This is an update of a review first published in 2004 and updated in 2006 and 2010.
OBJECTIVES
To evaluate the benefits and harms of different interventions used in children with idiopathic nephrotic syndrome, who do not achieve remission following four weeks or more of daily corticosteroid therapy.
SEARCH METHODS
We searched Cochrane Kidney and Transplant's Specialised Register (up to 2 March 2016) through contact with the Information Specialist using search terms relevant to this review.
SELECTION CRITERIA
RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS.
DATA COLLECTION AND ANALYSIS
Two authors independently searched the literature, determined study eligibility, assessed risk of bias and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model.
MAIN RESULTS
Nineteen RCTs (820 children enrolled; 773 evaluated) were included. Most studies were small. Eleven studies were at low risk of bias for allocation concealment and only four studies were at low risk of performance bias. Fifteen, eight and 10 studies were at low risk of detection bias, attrition bias and reporting bias respectively. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission. However this was based on only eight children who achieved remission with cyclosporin compared with no children who achieved remission with placebo/no treatment in three small studies (49 children: RR 7.66, 95% CI 1.06 to 55.34). Calcineurin inhibitors significantly increased the number with complete or partial remission compared with IV cyclophosphamide (2 studies, 156 children: RR 1.98, 95% CI 1.25 to 3.13; I = 20%). There was no significant differences in the number who achieved complete remission between tacrolimus versus cyclosporin (1 study, 41 children: RR 0.86, 95% CI 0.44 to 1.66), cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study, 138 children: RR 2.14, 95% CI 0.87 to 5.24), oral cyclophosphamide with prednisone versus prednisone alone (2 studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (1 study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide plus IV dexamethasone (1 study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), and azathioprine with prednisone versus prednisone alone (1 study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). One study found no significant differences between three agents (cyclophosphamide, mycophenolate mofetil, leflunomide) used in combination with tacrolimus and prednisone. One study found no significant difference in the percentage reduction in proteinuria (31 children: -12; 95% CI -73 to 110) between rituximab with cyclosporin/prednisolone and cyclosporin/prednisolone alone. Two studies reported ACEi significantly reduced proteinuria.
AUTHORS' CONCLUSIONS
To date RCTs have demonstrated that calcineurin inhibitors increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide. For other regimens assessed, it remains uncertain whether the interventions alter outcomes because the certainty of the evidence is low. Further adequately powered, well designed RCTs are needed to evaluate other regimens for children with idiopathic SRNS. Since SRNS represents a spectrum of diseases, future studies should enrol children from better defined groups of patients with SRNS.
Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Dexamethasone; Drug Resistance; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Isoxazoles; Leflunomide; Mycophenolic Acid; Nephrotic Syndrome; Prednisone; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 27726125
DOI: 10.1002/14651858.CD003594.pub5 -
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 -
Rheumatology (Oxford, England) Mar 2021Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors... (Meta-Analysis)
Meta-Analysis
Prevalence and risk factors of relapse in patients with ANCA-associated vasculitis receiving cyclophosphamide induction: a systematic review and meta-analysis of large observational studies.
BACKGROUND
Clinical relapses are common in patients with ANCA-associated vasculitis (AAV). The aim of this systematic review was to estimate time-point prevalence and risk factors of relapse.
METHODS
We searched PubMed, Embase, and Cochrane Library databases from their inception to March 30, 2020. Cohorts and post-hoc studies were included for the estimation of summary cumulative relapse rates (CRRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Sensitivity and meta-regression analyses were also performed.
RESULTS
Of the 42 eligible studies, 24 studies with 6236 participants were used for the pooled analyses of CRRs. The summary 1-year, 3-year, and 5-year CRRs were 0.12 (95% CI, 0.10-0.14), 0.33 (0.29-0.38), and 0.47 (0.42-0.52), respectively. In meta-regressions, the baseline age was positively associated with 1-year CRR. The proportion of granulomatosis with polyangiitis was positively associated with 5-year CRR. Twenty-eight studies with 5390 participants were used for the meta-analysis of risk factors for relapse, including a lower level of baseline serum creatine, proteinase 3 (PR3)-ANCA positivity at diagnosis, an ANCA rise, extrarenal organ involvement (including lung, cardiovascular, upper respiratory, and gastrointestinal involvement), intravenous (vs oral) cyclophosphamide induction, a shorter course of immunosuppressant maintenance, and maintenance with mycophenolate mofetil (vs azathioprine).
CONCLUSIONS
Our systematic review demonstrated that the 1-year, 3-year, and 5-year cumulative probabilities of relapse were ∼12%, 33%, and 47% in AAV patients receiving cyclophosphamide induction, respectively. Early identification of risk factors for relapse is helpful to the risk stratification of patients so as to achieve personalized treatment.
Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cyclophosphamide; Humans; Immunosuppressive Agents; Prevalence; Recurrence; Risk Factors
PubMed: 33677596
DOI: 10.1093/rheumatology/keaa667 -
Clinical Pharmacokinetics Jul 2023Busulfan is commonly used in the chemotherapy prior to hematopoietic cell transplantation (HCT). Busulfan has a narrow therapeutic window and a well-established...
BACKGROUND
Busulfan is commonly used in the chemotherapy prior to hematopoietic cell transplantation (HCT). Busulfan has a narrow therapeutic window and a well-established exposure-response relationship with important clinical outcomes. Model-informed precision dosing (MIPD) based on population pharmacokinetic (popPK) models has been implemented in the clinical settings. We aimed to systematically review existing literature on popPK models of intravenous busulfan.
METHODS
We systematically searched Ovid MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science databases from inception to December 2022 to identify original popPK models (nonlinear mixed-effect modeling) of intravenous busulfan in HCT population. Model-predicted busulfan clearance (CL) was compared using US population data.
RESULTS
Of the 44 eligible popPK studies published since 2002, 68% were developed predominantly in children, 20% in adults, and 11% in both children and adults. The majority of the models were described using first-order elimination or time-varying CL (69% and 26%, respectively). All but three included a body-size descriptor (e.g., body weight, body surface area). Other commonly included covariates were age (30%) and GSTA1 variant (15%). Median between-subject and between-occasion variabilities of CL were 20% and 11%, respectively. Between-model variabilities in predicted median CL were < 20% in all of the weight tiers (10-110 kg) in the simulation based on US population data.
CONCLUSION
Busulfan PK is commonly described using a first-order elimination or time-varying CL. A simple model with limited covariates were generally sufficient to attain relatively small unexplained variabilities. However, therapeutic drug monitoring may still be necessary to attain a narrow target exposure.
Topics: Child; Adult; Humans; Busulfan; Administration, Intravenous; Hematopoietic Stem Cell Transplantation; Body Surface Area; Drug Monitoring
PubMed: 37415003
DOI: 10.1007/s40262-023-01275-x -
JAMA Oncology Dec 2015Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we performed a network meta-analysis to identify the most effective adjuvant chemotherapy regimen.
OBJECTIVE
To find the most effective adjuvant therapy regimen for early-stage breast cancer.
DATA SOURCES
We searched MEDLINE, Embase, and the Cochrane Library for articles published before June 2015; the American Society of Clinical Oncology annual meeting abstracts from January 1983 through December 2014; and the American Association for Cancer Research annual meeting abstracts from January 1916 through December 2014. Additionally, we manually searched bibliographies for related references.
STUDY SELECTION
We included randomized clinical trials of adjuvant treatments for early-stage breast cancer that compared 2 or more of the following: no adjuvant chemotherapy; sequential anthracycline-cyclophosphamide and taxane (AC-T); concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens.
DATA EXTRACTION AND SYNTHESIS
We followed the PRISMA guidelines. Two investigators independently selected the articles and extracted information. Disagreements were resolved by discussion with another author. Quality was assessed by Cochrane risk-of-bias method. Data were pooled using random-effects models.
MAIN OUTCOMES AND MEASURES
We used network meta-analysis to test the most effective adjuvant therapy regimen in terms of overall survival (OS) by comparing regimens listed in the National Comprehensive Cancer Network guidelines and platinum-containing regimens.
RESULTS
We identified 24 trials. The TC and platinum-containing regimens had OS benefit similar to that of sequential AC-T (TC hazard ratio [HR], 0.93; 95% CI, 0.62-1.40; and platinum HR, 0.93; 95% CI, 0.66-1.31). Patients treated with CMF or AC had significantly worse OS than those treated with sequential AC-T (CMF HR, 1.56; 95% CI, 1.32-1.85; and AC HR, 1.22; 95% CI, 1.10-1.37). Platinum-containing regimens tended to be more toxic than sequential AC-T. The toxicity of TC was similar to or less than that of sequential AC-T. Meta-regression analysis showed that hormone receptor status did not impact the HRs for OS for any regimen.
CONCLUSIONS AND RELEVANCE
Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Chemotherapy, Adjuvant; Cisplatin; Cyclophosphamide; Docetaxel; Female; Fluorouracil; Humans; Platinum Compounds; Randomized Controlled Trials as Topic; Taxoids; Treatment Outcome
PubMed: 26402167
DOI: 10.1001/jamaoncol.2015.3062 -
Advances in Rheumatology (London,... Jun 2024To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
OBJECTIVE
To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
METHODS
Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.
RESULTS
All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy.
CONCLUSION
This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
Topics: Lupus Nephritis; Humans; Immunosuppressive Agents; Brazil; Societies, Medical; Creatinine; Proteinuria; Mycophenolic Acid; Antibodies, Monoclonal, Humanized; Rheumatology; Rituximab; Biopsy; Cyclophosphamide; Leflunomide; Glucocorticoids; Hydroxychloroquine; Azathioprine; Remission Induction; Cyclosporine; Evidence-Based Medicine; Consensus; Disease Progression; Kidney Failure, Chronic; Randomized Controlled Trials as Topic
PubMed: 38890752
DOI: 10.1186/s42358-024-00386-8 -
Cancer Immunology, Immunotherapy : CII Apr 2023T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy... (Meta-Analysis)
Meta-Analysis Review
Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis.
BACKGROUND
T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy efficacy but is associated with significant toxicities. Evidence is sparse regarding the optimum LD regimen for TCR-T cell therapy in solid tumours.
METHODS
A systematic review was conducted of interventional, prospective clinical trials describing LD practices prior to TCR-T cell therapy in patients with advanced solid tumours. The objective was to define LD regimens administered prior to TCR-T cell therapy and their effects on specific safety and efficacy outcomes in this patient population.
RESULTS
Searches returned 484 studies, 19 (231 patients) met the eligibility criteria. Cyclophosphamide (cyclo) 60 mg/kg daily (2 days), plus fludarabine (fludara) 25 mg/m daily (5 days) was the most common LD regimen (38% of studies). Higher dose LD regimens were associated with increased pooled incidence rates of febrile neutropaenia compared to low dose (0.64, [95% Confidence interval (CI): 0.50-0.78], vs. 0.39 [95% CI: 0.25-0.53], respectively) but were not significantly associated with higher objective responses (odds ratio: 1.05, 95%CI: 0.60-1.82, p = 0.86). A major shortfall in safety data reporting was identified; determination of LD regimen effects on many safety outcomes was not possible.
CONCLUSION
Standard consensus guidelines for the design and reporting of adoptive cell therapy (ACT) studies would facilitate accurate risk-benefit analysis for optimising LD regimens in patients with advanced solid tumours.
Topics: Humans; Prospective Studies; Neoplasms; Cyclophosphamide; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 36315268
DOI: 10.1007/s00262-022-03287-1 -
Lupus Oct 2016Lupus nephritis (LN) is a significant cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE) and the severity of disease has been described... (Review)
Review
BACKGROUND
Lupus nephritis (LN) is a significant cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE) and the severity of disease has been described to be increased in Africans. Observational studies have been conducted; however, the treatment and outcome of African patients with LN has not been rigorously assessed.
METHODS
We conducted a systematic review of studies selected from a PubMed search of outcome in Africans with biopsy-proven LN from 1 January 1990 to 30 June 2015. Studies that gave information on histology, treatment and outcome of patients were included.
RESULTS
Sixteen studies were selected from a search that yielded 302 papers; half were from North Africa, 2/16 (12.5%) were prospective studies and 2/16 (12.5%) were multi-centre studies. The sample size of reported biopsies in the studies ranged from 22 to 246 patients. Only 3/16 (18.8%) studies used more recent criteria for the classification and reporting of renal histology, and proliferative LN (class III and IV) were reported with increased frequency from the studies. For induction therapy, all the studies reported use of corticosteroids while 15/16 (93.8%) of the studies also used cyclophosphamide (CYC) as an induction agent. Overall mortality rates ranged from 7.9% to 34.9% with increased disease activity, kidney failure and infections cited as common causes of mortality. Five-year renal survival was 48-84% while five-year patient survival was 54%-94%. Survival rates were higher for studies reported from North Africa.
CONCLUSION
This analysis highlights diagnostic challenges in LN in Africa and shows that a CYC/glucocorticoid-based regimen remains the standard of treatment for adult patients. The contributions of this therapy to reported outcomes of LN in Africa require further exploration.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Africa; Cyclophosphamide; Female; Humans; Lupus Nephritis; Male; Middle Aged; Standard of Care; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 27013662
DOI: 10.1177/0961203316640915 -
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