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Oncotarget Jul 2016We performed a network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of several intravesical chemotherapeutic (IVC) agents after... (Meta-Analysis)
Meta-Analysis Review
Single, immediate postoperative instillation of chemotherapy in non-muscle invasive bladder cancer: a systematic review and network meta-analysis of randomized clinical trials using different drugs.
We performed a network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of several intravesical chemotherapeutic (IVC) agents after transurethral resection of bladder tumor (TURB) in non-muscle invasive bladder cancer patients. The literature search was conducted using the Embase, Scopus and PubMed databases for RCTs, including patients with single or multiple, primary or recurrent stage Ta or T1 urothelial carcinoma of the bladder managed with a single, immediate instillation of IVC after TURB. Thirteen RCTs met the eligibility criteria. Pair-wise meta-analysis (direct comparison) showed that pirarubicin [hazard ratio (HR): 0.31], epirubicin (HR: 0.62), and MMC (HR: 0.40) were the most effective drugs for reducing tumor recurrence. Bayesian network meta-analysis (indirect comparison) revealed that treatment with pirarubicin (HR: 0.31), MMC (HR: 0.44), or epirubicin (HR: 0.60) was associated with prolonged recurrence-free survival. Among the drugs examined, only pirarubicin reduced disease progression compared to controls. These results suggest that a single, immediate administration of IVC with pirarubicin, MMC, or epirubicin is associated with prolonged recurrence-free survival following TURB in non-muscle invasive bladder cancer patients, though only pirarubicin also reduced disease progression.
Topics: Administration, Intravesical; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cyclophosphamide; Doxorubicin; Epirubicin; Humans; Melphalan; Network Meta-Analysis; Semustine; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 27323781
DOI: 10.18632/oncotarget.9991 -
PloS One 2015The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results... (Meta-Analysis)
Meta-Analysis Review
The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HD-DNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p<0.00001), OS(HR = 0.88, 95%CI[0.79,0.99], p = 0.002), and EFS (HR = 0.86, 95%CI [0.74, 1.00], p = 0.008), but not in DFS, relapse, and toxicity. There were no statistically significant differences in any other outcomes between HD-DNR and IDA. The analysis indicates that compared with LD-DNR, HD-DNR can significantly improve CR, OS and EFS but not DFS, and did not increase occurrence of relapse and toxicity.
Topics: Antibiotics, Antineoplastic; Daunorubicin; Dose-Response Relationship, Drug; Humans; Leukemia, Myeloid, Acute; Prospective Studies
PubMed: 25993000
DOI: 10.1371/journal.pone.0125612 -
Acta Haematologica 2015The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP).... (Meta-Analysis)
Meta-Analysis Review
The Role of Consolidative Radiotherapy after a Complete Response to Chemotherapy in the Treatment of Diffuse Large B-Cell Lymphoma in the Rituximab Era: Results from a Systematic Review with a Meta-Analysis.
BACKGROUND
The current standard therapy for patients with diffuse large B-cell lymphoma (DLBCL) is rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP). The role of radiotherapy (RT) after complete response (CR) to RCHOP in patients with DLBCL remains unclear. This systematic review with a meta-analysis is an attempt to evaluate this role.
METHODS
Studies that evaluated RT versus no-RT after CR to RCHOP for DLBCL patients were searched in databases. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were calculated using a random-effects model.
RESULTS
A total of 4 qualified retrospective studies (633 patients) were included in this review. The results suggested that RT improved overall survival (OS; HR 0.33, 95% CI 0.14-0.77) and progression-free/event-free survival (PFS/EFS; HR 0.24, 95% CI 0.11-0.50) in all patients compared with no-RT. In a subgroup analysis of patients with stage III-IV DLBCL, RT improved PFS/EFS (HR 0.19, 95% CI 0.07-0.51) and local control (HR 0.12, 95% CI 0.03-0.44), with a trend of improving OS (HR 0.35, 95% CI 0.12-1.05).
CONCLUSION
Consolidation RT could significantly improve outcomes of DLBCL patients who achieved a CR to RCHOP. However, the significance of these results was limited by these retrospective data. Further investigation of the role of consolidation RT in the rituximab era is needed.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Induction Chemotherapy; Lymphoma, Large B-Cell, Diffuse; Prednisone; Radiotherapy, Adjuvant; Retrospective Studies; Rituximab; Survival Analysis; Vincristine
PubMed: 25925586
DOI: 10.1159/000370096 -
British Journal of Haematology Jul 2015This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment (18) F-fluoro-2-deoxy-d-glucose positron... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed and meta-analysed the prognostic value of complete remission status at end-of-treatment (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R-CHOP-treated DLBCL patients who were in complete remission at end-of-treatment FDG-PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end-of-treatment FDG-PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression-free survival (PFS) of these patients at various specific time points, i.e., 2-year PFS (n = 1), estimated 3-year PFS (n = 3) and 5-year PFS (n = 1), which was 83%, 85-86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3-year OS (n = 2) and estimated 5-year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non-negligible proportion of R-CHOP-treated DLBCL patients who achieve complete remission according to end-of-treatment FDG-PET experiences disease relapse during follow-up.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Fluorodeoxyglucose F18; Humans; Lymphoma, Large B-Cell, Diffuse; Positron-Emission Tomography; Prednisone; Prognosis; Remission Induction; Rituximab; Treatment Outcome; Vincristine
PubMed: 25833790
DOI: 10.1111/bjh.13420 -
Health Technology Assessment... Jan 2015Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line... (Comparative Study)
Comparative Study Meta-Analysis Review
Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation.
BACKGROUND
Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer.
OBJECTIVES
To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer.
DATA SOURCES
Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013.
METHODS
A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed.
RESULTS
For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated.
LIMITATIONS
As platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease.
CONCLUSIONS
For platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013003555.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Deoxycytidine; Dioxoles; Disease-Free Survival; Double-Blind Method; Doxorubicin; Female; Health Care Costs; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Tetrahydroisoquinolines; Topotecan; Trabectedin; Treatment Outcome; United Kingdom; Gemcitabine
PubMed: 25626481
DOI: 10.3310/hta19070 -
The Cochrane Database of Systematic... Aug 2014Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES
To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA
Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS
We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS
The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.
Topics: Alitretinoin; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Bleomycin; Doxorubicin; Drug Therapy, Combination; Etoposide; HIV Infections; Humans; Liposomes; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sarcoma, Kaposi; Skin Neoplasms; Tretinoin; Vincristine
PubMed: 25221796
DOI: 10.1002/14651858.CD003256.pub2 -
The Cochrane Database of Systematic... May 2014Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.
OBJECTIVES
To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.
DATA COLLECTION AND ANALYSIS
Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.
MAIN RESULTS
We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.
AUTHORS' CONCLUSIONS
There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Doxorubicin; Endometrial Neoplasms; Female; Humans; Neoplasm Staging; Paclitaxel; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic
PubMed: 24832785
DOI: 10.1002/14651858.CD010681.pub2 -
BMJ Clinical Evidence Mar 2014Rhegmatogenous 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 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 September 2013 (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 14 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, daunorubicin, fluorouracil plus low molecular weight heparin, pneumatic retinopexy, scleral buckling, short-acting or long-acting gas tamponade, silicone oil tamponade, and vitrectomy.
Topics: Humans; Retinal Detachment; Vitreoretinopathy, Proliferative
PubMed: 24807890
DOI: No ID Found -
Cancer Biology & Therapy Jun 2014Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no... (Meta-Analysis)
Meta-Analysis Review
Ovarian cancer is the leading cause of death among gynecological tumors. Carboplatin/paclitaxel represents the cornerstone of front-line treatment. Instead, there is no consensus for management of recurrent/progressive disease, in which pegylated liposomal doxorubicin (PLD) ± carboplatin is widely used. We performed a systematic review and metaanalysis to evaluate impact of PLD-based compared with no-PLD-based regimens in the ovarian cancer treatment. Data were extracted from randomized trials comparing PLD-based treatment to any other regimens in the January 2000-January 2013 time-frame. Study end-points were overall survival (OS), progression free survival (PFS), response rate (RR), CA125 response, and toxicity. Hazard ratios (HRs) of OS and PFS, with 95% CI, odds ratios (ORs) of RR and risk ratios of CA125 response and grade 3-4 toxicity, were extracted. Data were pooled using fixed and random effect models for selected endpoints. Fourteen randomized trials for a total of 5760 patients were selected and included for the final analysis, which showed no OS differences for PLD-based compared with other regimens (pooled HR: 0.94; 95% CI: 0.88-1.02; P = 0.132) and a significant PFS benefit of PLD-based schedule (HR: 0.91; 95% CI: 0.86-0.96; P = 0.001), particularly in second-line (HR: 0.85; 95% CI: 0.75-0.91) and in platinum-sensitive (HR: 0.83; 95% CI: 0.74-0.94) subgroups. This work confirmed the peculiar tolerability profile of this drug, moreover no difference was observed for common hematological toxicities and for RR, CA125 response. PLD-containing regimens do not improve OS when compared with any other schedule in all phases of disease. A marginal PFS advantage is observed only in platinum-sensitive setting and second-line treatment.
Topics: Antibiotics, Antineoplastic; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Polyethylene Glycols; Proportional Hazards Models; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24658024
DOI: 10.4161/cbt.28557 -
The Cochrane Database of Systematic... Oct 2013Epithelial ovarian cancer (EOC) is often diagnosed at an advanced stage, requiring primary cytoreductive surgery and combination chemotherapy for its first-line... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epithelial ovarian cancer (EOC) is often diagnosed at an advanced stage, requiring primary cytoreductive surgery and combination chemotherapy for its first-line management. Currently, the recommended standard first-line chemotherapy is platinum-based, usually consisting of carboplatin and paclitaxel (PAC/carbo). Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin that is associated with fewer and less severe side effects than are seen with non-modified doxorubicin. In combination with carboplatin, PLD has recently been shown to improve progression-free survival compared with PAC/carbo in women with relapsed, platinum-sensitive EOC. It is therefore important to know whether any survival benefit can be attributed to PLD when it is used in the first-line setting.
OBJECTIVES
To evaluate the role of PLD, alone or in combination, in first-line chemotherapy for women with EOC.
SEARCH METHODS
We searched The Cochrane Gynaecological Cancer Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE from January 1990 to February 2013. In addition, we searched online trial registries for ongoing trials and abstracts of studies presented at relevant scientific meetings from 2000 onwards.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared PLD alone or in combination with other agent/s (e.g. carboplatin) versus other agent/s for first-line chemotherapy in women with EOC who may or may not have undergone primary cytoreductive surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data and assessed the risk of bias for each included trial. We obtained updated trial data when possible.
MAIN RESULTS
We included two large trials. One trial compared three-weekly PLD and carboplatin (PLD/carbo) with PAC/carbo. The other trial included four experimental arms, one of which was PLD plus PAC/carbo, that were compared with the standard PAC/carbo regimen. We did not combine results of these two trials in the meta-analysis. We considered the two studies to be at low risk of bias.For the comparison PLD/carbo versus PAC/carbo (820 women; stages Ic to IV), no statistically significant differences in progression-free survival (PFS) (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.85 to 1.19) or overall survival (OS) (HR 0.94, 95% CI 0.78 to 1.13) were noted between study arms. Severe anaemia (risk ratio [RR] 2.74, 95% CI 1.54 to 4.88) and thrombocytopenia (RR 8.09, 95% CI 3.93 to 16.67) were significantly more common with PLD/carbo, whereas alopecia (RR 0.09, 95% CI 0.06 to 0.14) and severe neurotoxicity (RR 0.09, 95% CI 0.01 to 0.66) were significantly more common with PAC/carbo. Quality of life scores were not significantly different.For the comparison PLD/PAC/carbo versus PAC/carbo (1726 women; stage III/IV), it is important to note that PLD was given for alternate cycles only (i.e. every 6 weeks). No statistically significant difference in PFS (HR 0.98, 95% CI 0.88 to 1.09) or OS (HR 0.95, 95% CI 0.84 to 1.08) between these two treatment arms was reported. However, women in the triplet arm experienced significantly more severe haematological adverse events (anaemia, thrombocytopenia, neutropenia and febrile neutropenia) compared with those given standard treatment.No RCTs evaluated single-agent PLD for first-line treatment of EOC.
AUTHORS' CONCLUSIONS
PLD/carbo is a reasonable alternative to PAC/carbo for the first-line treatment of EOC. Although three-weekly PLD/carbo may be associated with increased dose delays and discontinuations compared with the standard PAC/carbo regimen, it might be more acceptable to women who wish to avoid alopecia or those at high risk of neurotoxicity. No survival benefits appear to be associated with the alternating triplet regimen, and the additional toxicity associated with adding PLD to PAC/carbo limits further investigation. Further studies are needed to establish the safest, most effective PLD/carbo regimen for newly diagnosed disease.
Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Ovarian Epithelial; Doxorubicin; Drug Administration Schedule; Female; Humans; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 24142521
DOI: 10.1002/14651858.CD010482.pub2