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The Cochrane Database of Systematic... Jul 2013Ovarian cancer is the eighth most common cancer in women and it is usually diagnosed at an advanced stage. The majority of ovarian tumours are epithelial in origin.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ovarian cancer is the eighth most common cancer in women and it is usually diagnosed at an advanced stage. The majority of ovarian tumours are epithelial in origin. Women with relapsed epithelial ovarian cancer (EOC) often have a reduced performance status with a limited life expectancy, therefore maintaining quality of life with effective symptom control is the main purpose of treatment. Drug treatment of relapsed disease is directed by the platinum-free interval: relapsed platinum-sensitive disease is usually re-treated with platinum-based therapy and platinum-resistant disease challenged with non-platinum drugs. However, the side-effects of chemotherapy agents may be severe and optimal treatment regimens are unclear. Pegylated liposomal doxorubicin (PLD), which contains a cytotoxic drug called doxorubicin hydrochloride is one of several treatment modalities that may be considered for single-agent treatment of relapsed EOC, or used in combination with other drugs.
OBJECTIVES
To assess the efficacy and safety of PLD in women with relapsed epithelial ovarian cancer (EOC).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group (CGCG) trials register, CENTRAL, MEDLINE and EMBASE from 1990 to February 2013. We also searched online registers of clinical trials, abstracts of scientific meetings and reference lists of included studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that evaluated PLD in women diagnosed with relapsed epithelial ovarian cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data to a pre-designed data collection form and assessed the risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions guidelines. Where possible, we pooled collected data in meta-analyses using RevMan 5.2 software.
MAIN RESULTS
We included 14 RCTs that evaluated PLD alone or in combination with other drugs. Four RCTs contributed no data to the meta-analyses. Two studies compared PLD plus carboplatin (carbo) to paclitaxel (PAC)/carbo in women with platinum-sensitive relapsed EOC. Overall survival (OS) was similar for these treatments, however progression-free survival (PFS) was longer with PLD/carbo (1164 participants; hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.74 to 0.97; I² = 7%; P value 0.01). PLD/carbo was associated with significantly more anaemia and thrombocytopenia than PAC/carbo, whereas PAC/carbo was associated with significantly more alopecia, neuropathies, hypersensitivity reactions and arthralgias/myalgias. PLD/carbo was well-tolerated and women receiving this treatment were significantly less likely to discontinue treatment than those receiving PAC/carbo (two studies, 1150 participants; risk ratio (RR) 0.38, 95% CI 0.26 to 0.57; I² = 0%; P < 0.00001).Five studies compared other agents to PLD alone. None of these agents were associated with significantly better survival or severe adverse-event profiles than PLD. Topotecan and gemcitabine were associated with significantly more haematological severe adverse events than PLD, and patupilone was associated with significantly more severe neuropathies and diarrhoea. Severe hand-foot syndrome (HFS) occurred consistently more frequently with PLD than the other drugs.Three studies compared PLD combination treatment to PLD alone. Two combinations resulted in a significantly longer PFS compared with PLD alone: trabectedin (TBD)/PLD (one study, 672 women; HR 0.79, 95% CI 0.65 to 0.96; P value 0.02) and vintafolide (EC145)/PLD (one study, 149 women; HR 0.63, 95% CI 0.41 to 0.97; P value 0.04). TBD/PLD appeared to benefit the partially platinum-sensitive subgroup only. Further studies are likely to have an important impact on our confidence in these estimates. TBD/PLD was associated with significantly more haematological and gastrointestinal severe adverse events than PLD alone, whereas EC145/PLD appeared to be well-tolerated.For platinum-resistant relapsed EOC, the median PFS and OS for single-agent PLD across seven included studies was 15 weeks and 54 weeks, respectively. Severe HFS occurred significantly more frequently in women receiving a 50 mg/m² dose of PLD than those receiving less than 50 mg/m² (17% versus 2%, respectively; P value 0.01).
AUTHORS' CONCLUSIONS
In platinum-sensitive relapsed epithelial ovarian cancer, PLD/carbo is more effective than PAC/carbo and is better tolerated; PLD/carbo should therefore be considered as first-line treatment in women with platinum-sensitive relapsed EOC. PLD alone is a useful agent for platinum-resistant relapsed EOC, however it remains unclear how it compares with other single agents for this subgroup and in what order these agents should be used. There is insufficient evidence to support the use of PLD in combination with other agents in platinum-resistant relapsed EOC.
Topics: Antibiotics, Antineoplastic; Carcinoma, Ovarian Epithelial; Doxorubicin; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 23835762
DOI: 10.1002/14651858.CD006910.pub2 -
The Cochrane Database of Systematic... Jan 2013This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.
SEARCH METHODS
For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.
MAIN RESULTS
We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.
AUTHORS' CONCLUSIONS
CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Early Termination of Clinical Trials; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 23440800
DOI: 10.1002/14651858.CD005196.pub4 -
British Journal of Haematology Apr 2013This systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid... (Comparative Study)
Comparative Study Meta-Analysis Review
This systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid leukaemia in children and adults younger than 60 years of age. Twenty-nine randomized controlled trials were eligible for inclusion in the review. Idarubicin (IDA), in comparison to daunorubicin (DNR), reduced remission failure rates (risk ratio (RR) 0·81; 95% confidence interval (CI), 0·66-0·99; P = 0·04), but did not alter rates of early death or overall mortality. Superiority of IDA for remission induction was limited to studies with a DNR/IDA dose ratio <5 (ratio <5: RR 0·65; 95% CI, 0·51-0·81; P < 0·001; ratio ≥5: RR 1·03; 95% CI, 0·91-1·16; P = 0·63). Higher-dose DNR, compared to lower-dose DNR, was associated with reduced rates for remission failure (RR 0·75; 95% CI, 0·60-0·94; P = 0·003) and overall mortality (RR 0·83; 95% CI, 0·75-0·93; P < 0·001), but not for early death. Comparisons of several other anthracycline derivates did not reveal significant differences in outcomes. Survival estimates in adults suggest that both high-dose DNR (90 mg/m(2) daily × 3 or 50 mg/m(2) daily × 5) and IDA (12 mg/m(2) daily × 3) can achieve 5-year survival rates of between 40 and 50 percent.
Topics: Adult; Antibiotics, Antineoplastic; Child; Child, Preschool; Daunorubicin; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Idarubicin; Infant; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission Induction; Survival Rate
PubMed: 23398482
DOI: 10.1111/bjh.12233 -
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 -
The Cochrane Database of Systematic... Sep 2012Indolent B cell lymphoid malignancies include follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and marginal zone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Indolent B cell lymphoid malignancies include follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphomas. Chronic lymphocytic leukaemia (CLL) is a lymphoid malignancy similar to small lymphocytic lymphoma (SLL) in its leukaemic phase.Indolent lymphoid malignancies including CLL are characterised by slow growth, a high initial response rate and a relapsing and progressive disease course. Advanced-stage indolent B cell lymphoid malignancies are often incurable. If symptoms or progressive disease occur, chemotherapy plus rituximab is indicated. No chemotherapy regimen has been shown to improve overall survival compared to a different regimen.Bendamustine is efficacious in the treatment of patients with indolent B cell lymphoid malignancies. A number of randomised controlled trials have examined the effect of bendamustine compared to other chemotherapy regimens in these patients. Improved disease control with no survival benefit is shown.
OBJECTIVES
To evaluate the efficacy of bendamustine therapy for patients with indolent B cell lymphoid malignancies including CLL.
SEARCH METHODS
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966 to May 2012), EMBASE (1974 to November 2011), LILACS (1982 to May 2012), databases of ongoing trials (accessed 30 April 2012) and relevant conference proceedings. We searched references of identified trials and contacted the first author of each included trial.
SELECTION CRITERIA
Randomised controlled trials that compared a bendamustine-containing regimen to other chemotherapy with or without immunotherapy.
DATA COLLECTION AND ANALYSIS
Two authors independently appraised the quality of each trial and extracted data from included trials. We estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
We included five trials randomising 1343 adult patients in the systematic review. Allocation and blinding were unclear in three trials and adequate in two. Incomplete outcome data and selective reporting were adequate in all trials. Trials varied in the type of lymphoid malignancy, bendamustine regimen and the comparator regimen. In the three trials that included patients with follicular lymphoma, mantle cell lymphoma and other indolent lymphomas the comparator treatment was cyclophosphamide, a combination of cyclophosphamide, vincristine, doxorubicin and prednisone, and fludarabine. Two trials included only patients with CLL and compared bendamustine to chlorambucil, and to fludarabine. We did not conduct a meta-analysis due to the clinical heterogeneity among trials. Bendamustine had no statistically significant effect on the overall survival of patients with indolent B cell lymphoid malignancies in any of the included trials (trials of moderate quality). Progression-free survival was statistically significantly improved with bendamustine treatment compared to other chemotherapy in three of the four trials that reported on it. One trial demonstrated a non statistically significant improvement of PFS. The risk of grade 3 or 4 adverse events was similar when bendamustine was compared to CHOP and fludarabine, and higher when compared to chlorambucil. Compared to chlorambucil quality of life was unaffected by bendamustine treatment (one trial, no meta-analysis).
AUTHORS' CONCLUSIONS
As none of the currently available chemotherapeutic protocols for induction therapy in indolent B cell lymphoid malignancies confer a survival benefit and due to the improved progression-free survival in each of the included trials, and a similar rate of grade 3 or 4 adverse events, bendamustine may be considered for the treatment of patients with indolent B cell lymphoid malignancies. However, the unclear effect on survival and the higher rate of adverse events compared to chlorambucil in patients with CLL/SLL does not support the use of bendamustine for these patients.The effect of bendamustine combined with rituximab should be evaluated in randomised clinical trials with more homogenous populations and outcomes for specific subgroups of patients by type of lymphoma should be reported. Any future trial should evaluate the effect of bendamustine on quality of life.
Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Nitrogen Mustard Compounds; Prednisone; Recurrence; Vincristine; Waldenstrom Macroglobulinemia
PubMed: 22972131
DOI: 10.1002/14651858.CD009045.pub2 -
The Oncologist 2010To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of... (Comparative Study)
Comparative Study
Tolerability, efficacy, and safety of pegylated liposomal Doxorubicin in combination with Carboplatin versus gemcitabine-Carboplatin for the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review.
OBJECTIVE
To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature.
METHODS
Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem-Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies.
RESULTS
Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem-Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD-Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem-Carbo populations, respectively. The median OS was longer for the PLD-Carbo regimen (27.1 months) than for the Gem-Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem-Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem-Carbo, 62.9%) were more common in patients receiving Gem-Carbo.
CONCLUSION
Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem-Carbo for the treatment of patients with PSROC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Deoxycytidine; Disease-Free Survival; Doxorubicin; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Polyethylene Glycols; Gemcitabine
PubMed: 20930103
DOI: 10.1634/theoncologist.2009-0331 -
The Cochrane Database of Systematic... May 2010The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.
OBJECTIVES
To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients.
SEARCH STRATEGY
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults).
DATA COLLECTION AND ANALYSIS
Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects.
MAIN RESULTS
We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified.
AUTHORS' CONCLUSIONS
We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
Topics: Adult; Antibiotics, Antineoplastic; Cardiac Output, Low; Child; Doxorubicin; Epirubicin; Heart; Humans; Liposomes; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 20464735
DOI: 10.1002/14651858.CD005006.pub4 -
BMJ Clinical Evidence Nov 2010Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to... (Review)
Review
INTRODUCTION
Rhegmatogenous retinal detachment (RRD) is the most common form of retinal detachment, where a retinal "break" allows the ingress of fluid from the vitreous cavity to the subretinal space, resulting in retinal separation. It occurs in about 1 in 10,000 people a year.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent progression from retinal breaks or lattice degeneration to retinal detachment? What are the effects of different surgical interventions in people with rhegmatogenous retinal detachment? What are the effects of interventions to treat proliferative vitreoretinopathy occurring as a complication of retinal detachment or previous treatment for retinal detachment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: corticosteroids, cryotherapy, daunorubicin, fluorouracil plus low molecular weight heparin, laser photocoagulation, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy.
Topics: Humans; Incidence; Retinal Detachment; Scleral Buckling; Silicone Oils; Vitrectomy; Vitreoretinopathy, Proliferative
PubMed: 21406128
DOI: No ID Found -
Cancer Aug 2008The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of adjuvant chemotherapy to treat adults with localized resectable soft-tissue sarcoma remains controversial. The objective of this systematic review was to update the 1997 meta-analysis of randomized controlled trials (RCTs) to reassess the efficacy of doxorubicin-based chemotherapy with respect to recurrence and survival.
METHODS
A comprehensive literature search was performed to identify RCTs of adjuvant chemotherapy for adult patients diagnosed with localized resectable soft-tissue sarcoma. Two reviewers independently assessed eligibility and quality of the studies using a modified version of the Detsky Quality Scale. The outcome measures were local, distant, and overall recurrence and survival calculated through the fixed effect or random effect model.
RESULTS
Four new eligible trials were identified allowing for a total of 18 trials representing 1953 patients to be included in the analysis. The odds ratios (OR) for local recurrence was 0.73 (95% confidence interval [CI] 0.56-0.94; P = .02) in favor of chemotherapy. For distant and overall recurrence the OR was 0.67 (95% CI 0.56-0.82; P = .0001) in favor of chemotherapy. In terms of survival, doxorubicin alone had an OR of 0.84 (95% CI, 0.68-1.03; P = .09), which as not statistically significant. However, the OR for doxorubicin combined with ifosfamide was 0.56 (95% CI, 0.36-0.85; P = .01) in favor of chemotherapy.
CONCLUSIONS
This updated meta-analysis confirms the marginal efficacy of chemotherapy in localized resectable soft-tissue sarcoma with respect to local recurrence, distant recurrence, overall recurrence, and overall survival. These benefits are further improved with the addition of ifosfamide to doxorubicin-based regimens, but must be weighed against associated toxicities.
Topics: Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Odds Ratio; Randomized Controlled Trials as Topic; Sarcoma; Survival Analysis
PubMed: 18521899
DOI: 10.1002/cncr.23592 -
The Cochrane Database of Systematic... Apr 2008Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chemotherapeutic agents such as topotecan can be used to treat ovarian cancer. The effects of using topotecan as a therapeutic agent have not been previously been systematically reviewed.
OBJECTIVES
To systematically evaluate the effectiveness and safety of topotecan for the treatment of ovarian cancer.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 4, 2006); Cochrane Gynaecological Cancer Review Group (CGCRG) Specialised Register (Cochrane Library Issue 4, 2006); MEDLINE (January 1990 to 27 July 2006); EMBASE (January 1990 to 27 July 2006); The European Organization for the Research and Treatment of Cancer (EORTC) database (to 1 August 2006); CBM (Chinese Biomedical Database) (January 1990 to 27 July 2006).
SELECTION CRITERIA
Randomised controlled trials (RCTs) which randomized patients with ovarian cancer to single or combined use of topotecan versus interventions without topotecan, or different remedies of topotecan.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted and analysed data.
MAIN RESULTS
Six studies including 1323 participants were eligible for this review (Gordon 2004a; Gore 2001a; Gore 2002; Hoskins 1998; Huinink 2004; Placido 2004) All studies, as reported, were identified as being of poor methodological quality. Topotecan had comparable effectiveness to prolong progression-free survival (PFS) compared with pegylated liposomal doxorubicin (PLD), (16.1 weeks versus 17.0 weeks; p = 0.095). Overall survival (OS) time was similar in participants using PLD compared with topotecan (56.7 weeks versus 60 weeks; p = 0.341). Topotecan was more hematologically toxic compared with paclitaxel or PLD, relative risks (RRs) of hematological events: ranged from 1.03 to 14.46 and 1.73 to 27.12 respectively. A 21-day cycle of topotecan was more toxic than a 42-day cycle (RRs of hematological and non-hematological events ranged from 1.03 to 8). Intravenous and oral topotecan had comparable toxicity. Topotecan delayed progression more effectively compared with paclitaxel (23.1 weeks versus 14 weeks, p = 0.0021). Participants were more likely to respond to topotecan on a 21-day cycle as opposed to a 42-day cycle (RR 7.23, 95% CI 0.94 to 55.36). Small tumor diameter, sensitivity to platinum-based chemotherapy was associated with better prognosis. Small sample size, methodological flaws and poor reporting of the included trials made measurement bias of the trials difficult to assess.
AUTHORS' CONCLUSIONS
Topotecan appears to have a similar level of effectiveness as paclitaxel and PLD, though with different patterns of side effects. Larger, well-designed RCTs are required in order to define an optimal regime.
Topics: Antineoplastic Agents; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic; Topotecan
PubMed: 18425923
DOI: 10.1002/14651858.CD005589.pub2