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Health Technology Assessment... Jul 2007To evaluate the technologies used to reduce anthracycline-induced cardiotoxicity in children. Also to evaluate cardiac markers to quantify cardiotoxicity, and identify... (Review)
Review
OBJECTIVES
To evaluate the technologies used to reduce anthracycline-induced cardiotoxicity in children. Also to evaluate cardiac markers to quantify cardiotoxicity, and identify cost-effectiveness studies and future research priorities.
DATA SOURCES
Eight electronic databases were searched from inception to January 2006. Bibliographies of related papers were assessed for relevant studies and experts contacted to identify additional published references.
REVIEW METHODS
A systematic review of the evidence was undertaken using a priori methods.
RESULTS
Four randomised controlled trials (RCTs) met the inclusion criteria of the review, each considering a different cardioprotective intervention; all trials included children with acute lymphoblastic leukaemia, and one also included children with non-Hodgkin's lymphoma. However, all had methodological limitations. No cost-effectiveness studies were identified. One RCT and six cohort studies on the use of cardiac markers met the inclusion criteria of the review, but also had methodological limitations. Of the two RCTs that considered continuous infusion versus bolus (rapid) infusion, one found that continuous infusion of doxorubicin did not offer any cardioprotection over bolus; the other suggested that continuous infusion of daunorubicin had less cardiotoxicity than bolus. Two studies considered cardioprotective agents, one concluded that dexrazoxane prevents or reduces cardiac injury without compromising the antileukaemic efficacy of doxorubicin and the other reported a protective effect of coenzyme Q10 on cardiac function during anthracycline therapy. One RCT suggested that cardiac troponin T can be used to assess the effectiveness of the cardioprotective agent dexrazoxane. Two cohort studies considering atrial natriuretic peptide and two considering brain (B-type) natriuretic peptide suggested that these chemicals are elevated in some subgroups of children treated with anthracyclines for cancer. N-terminal B-type natriuretic peptide levels were significantly elevated in children treated with anthracyclines who had cardiac dysfunction. One cohort study found that serum lipid peroxide was higher in younger children treated with doxorubicin than correspondingly aged children not receiving doxorubicin. No differences in carnitine levels were found in children treated with doxorubicin and a group of healthy children in one cohort study.
CONCLUSIONS
It is difficult to draw conclusions about the effectiveness of technologies for reducing or preventing cardiotoxicity and about the use of cardiac markers in children as the evidence is limited in quantity and quality. The lack of standardisation for monitoring and reporting cardiac performance is problematic. Not all studies report effectiveness in terms of cardiac outcomes and event-free survival with supporting statistical analyses. Studies are mostly small and of short duration, making generalisation difficult. Increasing numbers of survivors of childhood cancer treated with anthracyclines will experience cardiac damage and require long-term surveillance and management. This will have an impact on cardiac services and costs. Diverse medical problems and other late sequelae that affect cardiac outcome will have an impact on other specialist services. Mechanisms to reduce or prevent cardiotoxicity from anthracycline therapy and cardiac markers to improve monitoring could alter the extent of this impact on service provision. RCTs of the different methods for reducing or preventing cardiotoxicity in children treated with anthracyclines for cancer with long-term follow-up are needed to determine whether the technologies influence the development of cardiac damage. Cost-effectiveness research is also required.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiovascular Agents; Child; Drug Administration Schedule; Heart Diseases; Heart Failure; Humans; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 17610809
DOI: 10.3310/hta11270 -
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 -
Annals of Oncology : Official Journal... May 2007In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus... (Clinical Trial)
Clinical Trial Review
BACKGROUND
In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus indolent biologic behavior of the neoplasm. The overall median survival was approximately 1 year after systemic chemotherapy. Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established.
PATIENTS AND METHODS
Searches for relevant studies published in peer-reviewed medical journals on CRS and PIC for DMPM before May 2006 were carried out on six databases. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. Expert academic surgeons in Washington, DC, USA were asked whether they knew about any important unpublished data. Two investigators independently evaluated each study according to predefined criteria. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies.
RESULTS
Seven prospective observational studies from six tertiary institutions were available, allowing 240 DMPM patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. The perioperative morbidity varied from 25% to 40% and mortality ranged from 0% to 8%.
CONCLUSIONS
This systematic review evaluated the current evidence for CRS and PIC for DMPM. Seven observational studies were available for assessment, which demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Asbestos; Cisplatin; Combined Modality Therapy; Doxorubicin; Follow-Up Studies; Humans; Infusions, Parenteral; Mesothelioma; Peritoneal Neoplasms; Survival Analysis; Time Factors; Treatment Outcome
PubMed: 17130182
DOI: 10.1093/annonc/mdl428 -
International Journal of... 2006Kaposi's sarcoma (KS) is a form of skin cancer that can involve internal organs. It is often found in patients with acquired immunodeficiency syndrome (AIDS) and can be... (Review)
Review
Kaposi's sarcoma (KS) is a form of skin cancer that can involve internal organs. It is often found in patients with acquired immunodeficiency syndrome (AIDS) and can be fatal. Kaposi's sarcoma produces pink, purple or brown tumors on the skin, mucous membranes or internal organs. Treatment goals for KS are simple: to reduce the severity of the symptoms, shrink tumors and prevent disease progression. Unfortunately, there is no single best treatment-plan that can achieve all these goals. With widespread KS lesions over the body surface or evidence of spreading to other parts of the body, the physicians need to treat the patients with systemic chemotherapy. A new class of drugs, called liposomal anthracyclines, appears to produce good results with fewer toxic side effects than more conventional cytotoxic drugs. One of these drugs, pegylated liposomal doxorubicin (PLD) has become the treatment of choice. This article summarizes all the studies with PLD in systemic Kaposi's sarcoma.
Topics: Anthracyclines; Clinical Trials as Topic; Doxorubicin; Humans; Polyethylene Glycols; Sarcoma, Kaposi
PubMed: 16831292
DOI: 10.1177/039463200601900202 -
Health Technology Assessment... Mar 2006To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH)... (Review)
Review
Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer.
DATA SOURCES
Electronic databases covering publication years 2000-4. Company submissions.
REVIEW METHODS
Seventeen databases were searched for randomised controlled trials (RCTs) and systematic reviews for the clinical effectiveness of PLDH, topotecan and paclitaxel and economic evaluations of the cost-effectiveness of PLDH, topotecan and paclitaxel. Selected studies were quality assessed and data extracted, as were the three company submissions. A new model was developed to assess the costs of the alternative treatments, the differential mean survival duration and the impact of health-related quality of life. Monte-Carlo simulation was used to reflect uncertainty in the cost-effectiveness results.
RESULTS
Nine RCTs were identified. In five of these trials, both the comparators were used within their licensed indications. Of these five, three included participants with both platinum-resistant and platinum-sensitive advanced ovarian cancer, and a further two only included participants with platinum-sensitive disease. The comparators that were assessed in the three trials that included both subtypes of participants were PLDH versus topotecan, topotecan versus paclitaxel and PLDH versus paclitaxel. In the further two trials that included participants with the subtype of platinum-sensitive disease, the comparators that were assessed were single-agent paclitaxel versus a combination of cyclophosphamide, doxorubicin and cisplatin (CAP) and paclitaxel plus platinum-based chemotherapy versus conventional platinum-based therapy alone. A further four trials were identified and included in the review in which one of the comparators in the trial was used outside its licensed indication. The comparators assessed in these trials were oxaliplatin versus paclitaxel, paclitaxel given weekly versus every 3 weeks, paclitaxel at two different dose levels and oral versus intravenous topotecan. Four studies met the inclusion criteria for the cost-effectiveness review. The review of the economic evidence from the literature and industry submissions identified a number of significant limitations in existing studies assessing the cost-effectiveness of PLDH, topotecan and paclitaxel. Analysis 1 assessed the cost-effectiveness of PLDH, topotecan and paclitaxel administered as monotherapies. Sensitivity analysis was undertaken to explore the impact of patient heterogeneity (e.g. platinum-sensitive and platinum-resistant/refractory patients), the inclusion of additional trial data and alternative assumptions regarding treatment and monitoring costs. In the base-case results for Analysis 1, paclitaxel monotherapy emerged as the cheapest treatment. When the incremental cost-effectiveness ratios (ICERs) were estimated, topotecan was dominated by PLDH. Hence the options considered in the estimation of the ICERs were paclitaxel and PLDH. The ICER for PLDH compared with paclitaxel was pound 7033 per quality-adjusted life-year (QALY) in the overall patient population (comprising platinum-sensitive, -refractory and -resistant patients). The ICER was more favourable in the platinum-sensitive group ( pound 5777 per QALY) and less favourable in the platinum-refractory/resistant group ( pound 9555 per QALY). The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of the additional trial data resulted in less favourable estimates for the ICER for PLDH versus paclitaxel compared with the base-case results. The ICER of PLDH compared with paclitaxel was pound 20,620 per QALY in the overall patient population, pound 16,183 per QALY in the platinum-sensitive population and pound 26,867 per QALY in the platinum-resistant and -refractory population. The results from Analysis 2 explored the cost-effectiveness of the full range of treatment comparators for platinum-sensitive patients. The treatment options considered in this model comprised PLDH, topotecan, paclitaxel-monotherapy, CAP, paclitaxel/platinum combination therapy and platinum monotherapy. Owing to the less robust approaches that were employed to synthesise the available evidence and the heterogeneity between the different trials, the reliability of these results should be interpreted with some caution. Topotecan, paclitaxel monotherapy and PLDH were all dominated by platinum monotherapy (i.e. higher costs and lower QALYs). After excluding these alternatives, the treatments that remained under consideration were platinum monotherapy, CAP and paclitaxel-platinum combination therapy. Of these three alternatives, platinum monotherapy was the least costly and least effective. The ICER for CAP compared with platinum monotherapy was pound 16,421 per QALY. The ICER for paclitaxel-platinum combination therapy compared with CAP was pound 20,950 per QALY.
CONCLUSIONS
For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs. For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient's ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to pound 20,000-40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered. The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Liposomes; Ovarian Neoplasms; Paclitaxel; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Analysis; Topotecan
PubMed: 16545208
DOI: 10.3310/hta10090 -
British Journal of Cancer Nov 2005Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate... (Meta-Analysis)
Meta-Analysis
Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC). From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R(2)=34%), complete tumour response (P=0.02, R(2)=12%), progressive disease (P<0.001, R(2)=38%) and time to progression (P<0.0001, R(2)=56%); R(2) is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Cyclophosphamide; Disease Progression; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Randomized Controlled Trials as Topic; Regression Analysis; Survival Analysis
PubMed: 16278665
DOI: 10.1038/sj.bjc.6602858 -
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 -
The Cochrane Database of Systematic... 2003Considerable controversy exists as to whether any benefit of doxorubicin-based combination chemotherapy outweighs increased toxic effects, inconvenience, and additional... (Review)
Review
BACKGROUND
Considerable controversy exists as to whether any benefit of doxorubicin-based combination chemotherapy outweighs increased toxic effects, inconvenience, and additional costs, compared to single-agent doxorubicin. There is substantial variation in clinical practice in the treatment of patients with locally advanced and metastatic soft tissue sarcoma (STS).
OBJECTIVES
To determine:1) the effect, if any on response rate or survival, by using doxorubicin-based combination chemotherapy compared with single-agent doxorubicin for the treatment of patients with incurable locally advanced or metastatic STS2)if combination chemotherapy is associated with increased adverse effects compared with single-agent doxorubicin in this setting.
SEARCH STRATEGY
We searched CENTRAL (Cochrane Library, issue 4, 2002), MEDLINE (1966 to October 2002), CANCER LIT (1975 to October 2002), reference lists, the Physician Data Query (PDQ) clinical trials database, and the American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings (1995 to 2002).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing single-agent doxorubicin with doxorubicin-based combination chemotherapy in adults with locally advanced or metastatic STS requiring palliative chemotherapy. Abstracts and full reports published in English were eligible.
DATA COLLECTION AND ANALYSIS
Data were abstracted and assessed by two reviewers. Response and survival data were pooled. Data on adverse effects was tabulated.
MAIN RESULTS
Data on 2281 participants from eight RCTs were available from reports of single-agent doxorubicin versus doxorubicin-based combination chemotherapy. Meta-analysis using the fixed effect model detected a higher tumour response rate with combination chemotherapy compared with single-agent chemotherapy (odds ratio [OR= 1.29; 95% confidence interval [CI], 1.03 to 1.60; p = 0.03), but the OR from a pooled analysis using the random effects model and the same data did not achieve statistical significance (OR= 1.26; 95% CI, 0.96 to 1.67; p = 0.10). No significant difference between the two regimens was detected in the pooled one-year mortality rate (OR = 0.87; 95% CI, 0.73 to 1.05; p=0.14) or two-year mortality rate (OR = 0.84; 95% CI, 0.67 to 1.06; p=0.13) (N=2097). Although reporting of adverse effects was limited and inconsistent among trials (making pooling of data for this outcome impossible), adverse effects such as nausea/vomiting and hematologic toxic effects were consistently reported as being worse with combination chemotherapy across the eight eligible studies.
REVIEWER'S CONCLUSIONS
Compared to single-agent doxorubicin, the combination chemotherapy regimens evaluated, given in conventional doses, produced only marginal increases in response rates, at the expense of increased toxic effects and with no improvements in overall survival.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Palliative Care; Sarcoma
PubMed: 12917960
DOI: 10.1002/14651858.CD003293 -
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 -
Annals of Oncology : Official Journal... Apr 2002Anthracyclines are essential for the treatment of the children with cancer. We performed a systematic review to evaluate the existing evidence of the frequency and risk... (Review)
Review
BACKGROUND
Anthracyclines are essential for the treatment of the children with cancer. We performed a systematic review to evaluate the existing evidence of the frequency and risk factors of anthracycline-induced clinical heart failure (A-CHF) in children.
DESIGN
Medline was searched for articles reporting the frequency of A-CHF, published from 1966 to December 2000. Information about study features, risk factors and frequency were abstracted, and a validity score was given for each study. The potential predictive factors of A-CHF were analysed both within and across the studies.
RESULTS
The frequency of A-CHF in children was estimated in 30 studies described in 25 articles. All studies have serious methodological limitations. The frequency varied between 0% and 16%. In the analysis across the studies the type of anthracyclines and the maximal dose in 1 week explain a considerable part of the variation of the frequency of A-CHF.
CONCLUSIONS
Doxorubicin and a dose above 45 mg/m2 within 1 week seemed to increase the frequency of A-CHF. Well designed and executed studies are needed to accurately estimate the frequency of A-CHF and reliably assess the importance of potential risk factors.
Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Cardiovascular Diseases; Child; Child, Preschool; Dose-Response Relationship, Drug; Doxorubicin; Female; Forecasting; Humans; Infant; Infant, Newborn; Male; Neoplasms; Risk Factors
PubMed: 12056699
DOI: 10.1093/annonc/mdf118