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Molecules (Basel, Switzerland) Oct 2021Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer...
Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer drugs. At present, there is no other systematic review that assesses the potency of zeolites/ZIFs as anticancer drug carriers. Due to the porous nature and inherent pH-sensitive properties of zeolites/ZIFs, the compounds can entrap and selectively release anticancer drugs into the acidic tumor microenvironment. Therefore, it is valuable to provide a comprehensive overview of available evidence on the topic to identify the benefits of the compound as well as potential gaps in knowledge. The purpose of this study was to evaluate the potential therapeutic applications of zeolites/ZIFs as drug delivery systems delivering doxorubicin (DOX), 5-fluorouracil (5-FU), curcumin, cisplatin, and miR-34a. Following PRISMA guidelines, an exhaustive search of PubMed, Scopus, Embase, and Web of Science was conducted. No language or time limitations were used up to 25th August 2021. Only full text articles were selected that pertained to the usage of zeolites/ZIFs in delivering anticancer drugs. Initially, 1279 studies were identified, of which 572 duplicate records were excluded. After screening for the title, abstract, and full texts, 53 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for the 53 articles. The included studies suggest that anticancer drug-incorporated zeolites/ZIFs can be used as alternative treatment options to enhance the efficacy of cancer treatment by mitigating the drawbacks of drugs under conventional treatment.
Topics: Animals; Antineoplastic Agents; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Humans; Hydrogen-Ion Concentration; Male; Nanoparticles; Neoplasms; Porosity; Tumor Cells, Cultured; Tumor Microenvironment; Zeolites
PubMed: 34684777
DOI: 10.3390/molecules26206196 -
British Journal of Cancer Jan 2007This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children... (Review)
Review
This review systematically assessed the evidence on the clinical and cost-effectiveness of cardioprotection against the toxic effects of anthracyclines given to children with cancer. We searched eight electronic databases, including Medline and the Cochrane Library, from inception to January 2006 for systematic reviews and randomised controlled trials that reported death, heart failure, arrhythmias or measures of cardiac performance associated with cardioprotective technologies compared with standard treatment in children treated for cancer with anthracyclines. Economic evaluations were also sought. Inclusion criteria, data extraction and quality assessment were undertaken by standard methodology. Four randomised controlled trials met the inclusion criteria of the review; each had methodological limitations. No economic evaluations were identified. Studies were combined through narrative synthesis. One trial found that continuous infusion of doxorubicin did not offer any cardioprotection over rapid infusion. One suggested that continuous infusion of daunorubicin provoked less cardiotoxicity than rapid infusion. One concluded that dexrazoxane reduces cardiac injury during doxorubicin therapy and one reported a protective effect of coenzyme Q(10) on cardiac function during anthracycline therapy. The evidence on the effectiveness of cardioprotective technologies in children is limited in quality and quantity thus making conclusions difficult. This is surprising given the importance of anthracycline use in children with cancer. Further long-term research, which includes relevant outcome measures, is needed to determine whether technologies influence the development of cardiac damage without limiting the antitumour efficacy of anthracyclines.
Topics: Anthracyclines; Cardiotonic Agents; Child; Humans; State Medicine
PubMed: 17242696
DOI: 10.1038/sj.bjc.6603562 -
Advances in Clinical and Experimental... May 2024Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best therapeutic option for the treatment of osteosarcoma has not yet been determined.
OBJECTIVES
This meta-analysis was designed to assess the clinical efficacy of a high-dose methotrexate, doxorubicin and cisplatin (MAP) regimen and compare its survival outcomes with those of other chemotherapy strategies in patients diagnosed with osteosarcoma.
MATERIAL AND METHODS
We systematically searched databases, namely Embase, the Cochrane Library and PubMed, up to August 2022, for relevant studies investigating the impact of the MAP chemotherapy protocol on survival among patients with osteosarcoma. The odds ratio (OR) pooled estimates and their 95% confidence intervals (95% CIs) were calculated.
RESULTS
Twelve studies including 4102 patients were eligible for analysis in this study. The estimated pooled ORs of the 3-year overall survival (OS) and event-free survival (EFS) were OR = 1.08 (95% CI: 0.72-1.62, p = 0.70) and OR = 1.04 (95% CI: 0.81-1.32, p = 0.78, respectively). The 5-year OS and EFS were OR = 0.87 (95% CI: 0.62-1.23, p = 0.42) and OR = 1.13 (95% CI: 0.76-1.68, p = 0.54), respectively, with no statistical differences. The subgroup analysis of MAP compared to a 2-drug regimen (doxorubicin and cisplatin) revealed a significant difference between the 2 chemotherapy strategy groups in 3-year OS rates (OR = 0.72 (95% CI: 0.56-0.92, p = 0.009)) and 5-year EFS rates (OR = 0.57 (95% CI: 0.43-0.76, p < 0.001)).
CONCLUSION
The MAP chemotherapy strategy for osteosarcoma showed superiority over other regimens, especially over the 2-drug regimen (doxorubicin/cisplatin), in terms of better prognosis and safety.
Topics: Osteosarcoma; Humans; Cisplatin; Doxorubicin; Bone Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Methotrexate; Treatment Outcome; Antineoplastic Agents
PubMed: 37747442
DOI: 10.17219/acem/170098 -
The Neurologist Nov 2016There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial... (Review)
Review
INTRODUCTION
There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial given its reversibility with appropriate supportive management. We report a patient presenting with PRES after treatment with Rituximab, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone (R-CHOP) and intrathecal methotrexate. We also perform a systematic review of the literature on chemotherapy-associated PRES.
CASE REPORT
A 72-year-old man with recently diagnosed diffuse large B-cell lymphoma became unresponsive 4 days after initiation of R-CHOP and intrathecal methotrexate. Brain magnetic resonance imaging showed interval development of occipital and temporal fluid attenuation inversion recovery hyperintensities consistent with PRES. The patient's blood pressure was aggressively controlled and he received 5 days of high-dose methylprednisone. He subsequently regained consciousness and his mental status gradually improved. Repeat magnetic resonance imaging showed interval resolution of the bilateral fluid attenuation inversion recovery hyperintensities.
REVIEW SUMMARY
We performed a systematic review of the literature and included a total of 70 unique cases involving chemotherapy-associated PRES. Platinum-containing drugs, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone/R-CHOP regimens, and gemcitabine were the agents most commonly used in patients who developed suspected chemo-associated PRES. Median onset of symptoms occurred 8 days after chemotherapy. Hypertension was the most commonly reported risk factor associated with the development of chemotherapy-associated PRES. In most cases, PRES improved with supportive management alone within 2 weeks.
CONCLUSIONS
Chemotherapy-associated PRES is an increasingly encountered syndrome. Both neurologists and non-neurologists should be familiar with the most commonly implicated agents, symptoms, risk factors, and clinical course of chemotherapy-associated PRES, given its favorable prognosis with appropriate management.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Brain; Cyclophosphamide; Doxorubicin; Humans; Infusions, Spinal; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Methotrexate; Posterior Leukoencephalopathy Syndrome; Prednisone; Rituximab; Vincristine
PubMed: 27801773
DOI: 10.1097/NRL.0000000000000105 -
The Cochrane Database of Systematic... May 2017There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP... (Meta-Analysis)
Meta-Analysis Review
Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.
BACKGROUND
There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen.
OBJECTIVES
To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment.
SEARCH METHODS
We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL.
DATA COLLECTION AND ANALYSIS
The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials.
MAIN RESULTS
We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We included all five trials with 3427 people in the meta-analyses: the HD9 and HD14 trials were co-ordinated in Germany, the HD2000 and GSM-HD trials were performed in Italy and the EORTC 20012 was conducted in Belgium. The overall risk of performance and detection bias was low for overall survival (OS), but was high for other outcomes, as therapy blinding was not feasible. The remaining 'Risk of bias' domains were low and unclear.All trials reported results for OS and progression-free survival (PFS). In contrast to the our first published review (2011) the addition of results from the EORTC 20012 BEACOPP escalated increases OS (3142 participants; HR 0.74 (95% confidence interval (CI) 0.57 to 0.97; high-quality evidence). This means that only 90 (70 to 117) patients will die after five years in the BEACOPP escalated arm compared to 120 in the ABVD arm. This survival advantage is also reflected in an increased PFS with BEACOPP escalated (3142 participants; HR 0.54 (95% CI 0.45 to 0.64); moderate-quality evidence), meaning that after five years only 144 (121 to 168) patients will experience a progress, relapse or death in the BEACOPP escalated arm compared to 250 in the ABVD arm.There is no evidence for a difference for treatment-related mortality (2700 participants, RR 2.15 (95% CI = 0.93 to 4.95), low-quality evidence).Although the occurrence of MDS or AML may increase with BEACOPP escalated (3332 participants, RR 3.90 (95% CI 1.36 to 11.21); low-quality evidence)), there is no evidence for a difference between both regimens for overall secondary malignancies (3332 participants, RR 1.00 (95% CI 0.68 to 1.48), low-quality evidence). However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours which would not be expected to show significance until around 15 years after treatment.We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured (106 participants, RR 1.37 (95% CI 0.83 to 2.26), very low-quality evidence). This is a very small sample, and the age of the patients was not detailed. No analysis of male fertility was provided.Five trials reported adverse events and the analysis shows that the escalated BEACOPP regimens probably causes more haematological toxicities WHO grade III or IV ((anaemia: 2425 participants, RR 10.67 (95% CI 7.14 to 15.93); neutropenia: 519 participants, RR 1.80 (95% CI 1.52 to 2.13); thrombocytopenia: 2425 participants, RR 18.12 (95% CI 11.77 to 27.92); infections: 2425 participants, RR 3.73 (95% CI 2.58 to 5.38), all low-quality evidence).Only one trial (EORTC 20012) planned to assess quality of life, however, no results were reported.
AUTHORS' CONCLUSIONS
This meta-analysis provides moderate- to high-quality evidence that adult patients between 16 and 60 years of age with early unfavourable and advanced stage HL benefit regarding OS and PFS from first-line chemotherapy including escalated BEACOPP. The proven benefit in OS for patients with advanced HL is a new finding of this updated review due to the inclusion of the results from the EORTC 20012 trial. Furthermore, there is only low-quality evidence of a difference in the total number of secondary malignancies, as the follow-up period might be too short to detect meaningful differences. Low-quality evidence also suggests that people treated with escalated BEACOPP may have a higher risk to develop secondary AML or MDS. Due to the availability of only very low-quality evidence available, we are unable to come to a conclusion in terms of infertility. This review does for the first time suggest a survival benefit. However, it is clear from this review that BEACOPP escalated may be more toxic that ABVD, and very important long-term side effects of second malignancies and infertility have not been sufficiently analysed yet.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease Progression; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Middle Aged; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Young Adult
PubMed: 28541603
DOI: 10.1002/14651858.CD007941.pub3 -
Health Technology Assessment... Sep 2004To determine the clinical and cost-effectiveness of adding rituximab to the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy regime for adult... (Review)
Review
OBJECTIVES
To determine the clinical and cost-effectiveness of adding rituximab to the CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy regime for adult patients with diffuse large B-cell lymphoma (DLBCL).
DATA SOURCES
Electronic bibliographic database.
REVIEW METHODS
Comparative studies were selected for review if they addressed the clinical or cost-effectiveness of adding rituximab to CHOP in people aged at least 18 years with DLBCL. The internal validity of the study was assessed through the use of the validated Jadad scoring system. Data were abstracted into standardised data extraction forms. Costs were estimated through resource use data taken from the published trial and the unpublished sponsor submission. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to evaluate the cost-effectiveness of R-CHOP compared with CHOP alone for patients with DLBCL using data sources and methodology similar to the manufacturer's submission.
RESULTS
In the systematic review of effectiveness, one randomised controlled trial was identified. The study was, in most respects, methodologically rigorous and well conducted and the statistical evidence favoured the addition of rituximab to CHOP. The total cost of rituximab with CHOP (R-CHOP) and CHOP alone estimated from the model developed by ScHARR was 14,456 pounds and 5773 pounds, respectively, for patients aged 60 years and over, and 15,181 pounds and 7311 pounds for patients aged less than 60 years over a 15-year time horizon. The ScHARR model estimated that the addition of rituximab to CHOP generated an additional 0.82 QALY at an extra cost of 8683 pounds compared with CHOP alone therapy over a 15-year time horizon, a cost/quality-adjusted life-year (QALY) ratio of 10,596 pounds for patients aged 60 years or more. For patients aged under 60 years, 1.05 QALY were generated at an additional cost of 7870 pounds, a cost/QALY ratio of 7533 pounds. Assuming that the societal value of a QALY was 30,000 pounds then R-CHOP is cost-effective compared with CHOP in the treatment of DLBCL.
CONCLUSIONS
In the short term, the addition of rituximab to the CHOP regimen increased the likelihood of a complete-response by 20% without a significant rise in the risk of a serious adverse event in people aged 60 years or older. Over a 2-year follow-up period, the intervention reduced the risk of death, progression or relapse by 45% and reduced the risk of death by 47% in this population. There is no direct evidence for the clinical effectiveness of adding rituximab to CHOP in the treatment of DLBCL in those aged 18-59 years, although data from phase I and II trials confirm its safety and efficacy in a preclinical setting. The cost-effectiveness modelling presented here has shown that rituximab in combination with CHOP chemotherapy regimen is likely to be considered a cost-effective treatment for DLBCL when compared with the current standard treatment, CHOP chemotherapy only. Analysis of quality of life (QoL) in the area of NHL is limited and only one cost-utility analysis for the treatment of CHOP in NHL was identified. Both the SCHARR and the manufacturer's models utilised QoL utility scores from an unpublished data source. Further research within this area would help to improve the robustness of QoL utility analysis within DLBCL and also NHL as a whole. Further clinical trials might also establish whether R-CHOP may replace peripheral blood stem cell transplant in high-risk patients and whether the doses of chemotherapy in the elderly may be reduced if rituximab is added to less intensive regimens.
Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Cyclophosphamide; Data Collection; Doxorubicin; Drug Costs; Evidence-Based Medicine; Humans; Lymphoma, Large B-Cell, Diffuse; Needs Assessment; Neoplasm Staging; Peripheral Blood Stem Cell Transplantation; Prednisolone; Quality-Adjusted Life Years; Reproducibility of Results; Research Design; Risk Factors; Rituximab; Survival Analysis; Technology Assessment, Biomedical; Treatment Outcome; Value of Life; Vincristine
PubMed: 15361313
DOI: 10.3310/hta8370 -
Scientific Reports Apr 2018Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still... (Meta-Analysis)
Meta-Analysis
Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69-2.27)without heterogeneity(I = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43-1.89, I = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19-3.04, I = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Prednisone; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Rituximab; Survival Analysis; Vincristine
PubMed: 29674626
DOI: 10.1038/s41598-018-24631-5 -
Oxidative Medicine and Cellular... 2021Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse...
A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities.
PURPOSE
Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse effects on the normal cells/tissues, especially cardiotoxicity. The use of resveratrol may mitigate the doxorubicin-induced cardiotoxic effects. For this aim, we systematically reviewed the potential chemoprotective effects of resveratrol against the doxorubicin-induced cardiotoxicity.
METHODS
In the current study, a systematic search was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for the identification of all relevant studies on "the role of resveratrol on doxorubicin-induced cardiotoxicity" in the electronic databases of Web of Science, PubMed, and Scopus up to March 2021 using search terms in their titles and abstracts. Two hundred and eighteen articles were screened in accordance with a predefined set of inclusion and exclusion criteria. Finally, 33 eligible articles were included in this systematic review.
RESULTS
The and findings demonstrated a decreased cell survival, increased mortality, decreased heart weight, and increased ascites in the doxorubicin-treated groups compared to the control groups. The combined treatment of resveratrol and doxorubicin showed an opposite pattern than the doxorubicin-treated groups alone. Furthermore, this chemotherapeutic agent induced the biochemical and histopathological changes on the cardiac cells/tissue; however, the results (for most of the cases) revealed that these alterations induced by doxorubicin were reversed near to normal levels (control groups) by resveratrol coadministration.
CONCLUSION
The results of this systematic review stated that coadministration of resveratrol alleviates the doxorubicin-induced cardiotoxicity. Resveratrol exerts these chemoprotective effects through several main mechanisms of antioxidant, antiapoptosis, and anti-inflammatory.
Topics: Anti-Inflammatory Agents; Antioxidants; Apoptosis; Cardiotoxicity; Doxorubicin; Humans; Resveratrol
PubMed: 34471463
DOI: 10.1155/2021/2951697 -
Health Technology Assessment... 2012Follicular lymphoma (FL) is a non-Hodgkin's lymphoma which typically presents when the disease is at an advanced stage. The majority of patients receive first-line... (Review)
Review
BACKGROUND
Follicular lymphoma (FL) is a non-Hodgkin's lymphoma which typically presents when the disease is at an advanced stage. The majority of patients receive first-line therapy of rituximab in combination with chemotherapy, with two-thirds receiving cyclophosphamide, vincristine and prednisolone. The clinical and cost-effectiveness of other chemotherapies in combination with rituximab in first-line therapy is not known.
OBJECTIVE
To systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of rituximab (MabThera(®), Roche Products) in combination with chemotherapy, compared with chemotherapy alone, for the first-line treatment of symptomatic stage III-IV FL.
DATA SOURCES
A systematic review of literature and an economic evaluation were carried out. Key databases [including MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index to Nursing and Allied Health Literature (CINAHL); EMBASE; The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases; Science Citation Index (SCI); and BIOSIS], plus research registers and conference proceedings, were searched for relevant studies from inception up to October 2010.
REVIEW METHODS
One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. The quality of included studies was assessed by one reviewer and checked by a second. A patient-level simulation model was developed to estimate the costs and quality-adjusted life-year (QALY) gains from the perspective of the UK NHS and Personal Social Services, with costs and benefits discounted at 3.5% annually.
RESULTS
Four randomised controlled trials comparing rituximab plus chemotherapy (R-chemotherapy) with chemotherapy alone in untreated, symptomatic patients with stage III-IV FL were identified. R-chemotherapy compared with chemotherapy alone increased the likelihood of a response to treatment in all four trials, with no additional toxicity of clinical relevance. Overall response rates were significantly improved in all four trials, with a difference between the R-chemotherapy and chemotherapy arms of between 5% and 24%, respectively. Complete response rates were also improved, with a difference between the R-chemotherapy and chemotherapy arms of between 2% and 25%, respectively. Exploratory meta-analyses were conducted; the level of statistical heterogeneity was very high and thus we believe the response rates from the individual trials to be a more robust estimator of the efficacy of the specific R-chemotherapy regimens. Over a follow-up period of 4-5 years, R-chemotherapy significantly increased the overall survival rate compared with chemotherapy alone in three trials, although data for two trials were compromised owing to the use of additional treatments. The incremental cost-effectiveness ratio (ICER) for the addition of rituximab to CVP (cyclophosphamide, vincristine and prednisolone), CHOP (cyclophosphamide, doxorubicin/adriamycin, vincristine and prednisolone) and MCP [mitoxantrone, chlorambucil (Leukeran(®), Aspen) and prednisolone] was £7720, £10,834 and £9316 per QALY gained, respectively, when it was assumed that first-line rituximab maintenance was not used. A scenario analysis is also presented, assuming that responders to R-chemotherapy in first-line induction receive maintenance with rituximab, increasing the ICER to £14,959, £21,687 and £20,493 per QALY gained, respectively.
LIMITATIONS
These relate to the sources of data used for the effectiveness in first and second line and the assumed utility values; there is uncertainty about the effect of salvage treatment on patients who had been previously treated with an anthracycline regimen. There is uncertainty whether or not rituximab is as effective in second-line treatment when patients have been previously treated with rituximab.
CONCLUSIONS
The results from four randomised trials comparing R-chemotherapy with chemotherapy alone showed an improvement in clinical effectiveness outcomes, with minimal clinically relevant additional adverse events or toxicity. The cost per QALY gained is estimated to be < £25,000 for all three comparisons under our base-case assumption and is considerably lower if first-line rituximab maintenance is not assumed. More data on patients pre-treated with rituximab and on the effect of first-line maintenance with rituximab is required for future work.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cost-Benefit Analysis; Cyclophosphamide; Doxorubicin; England; Female; Humans; Lymphoma, Follicular; Male; Middle Aged; Mitoxantrone; Models, Economic; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Rituximab; Vincristine; Wales
PubMed: 23021127
DOI: 10.3310/hta16370 -
European Review For Medical and... Mar 2020We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.
We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 32271409
DOI: 10.26355/eurrev_202003_20655