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Leukemia & Lymphoma Nov 2004The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several... (Comparative Study)
Comparative Study Meta-Analysis Review
The superiority of Fludarabine over conventional therapy as primary induction therapy for patients with chronic lymphocytic leukemia (CLL) has been shown in several studies but no studies have yet reported a pooled estimate of the treatment effect. We performed a systematic review of evidence from 5 randomized controlled trials involving approximately 1300 patients with CLL, comparing Fludarabine with several alkylator-based combination regimens in the primary treatment of CLL. Complete response rate was significantly higher for Fludarabine compared to alkylator-based chemotherapy (RR 1.87, 95% CI 1.10-3.19, P=0.02), while overall response, though superior, did not reach statistical significance (RR 1.22, 95% CI=0.88-1.69, P=0.24). Overall survival was similar for Fludarabine and alkylator-based therapy (the pooled log hazard ratio of death, HR=-0.05, 95% CI=-0.36-0.26, P=0.75). Infection rate was significantly higher (RR 1.58, 95% CI=1.10-2.27, P=0.01), but there was no significant difference in the incidence of thrombocytopenia, neutropenia and anemia. Therefore, this meta-analysis supports the findings that Fludarabine as an induction agent for patients with CLL yields a better clinical response with acceptable toxicity when compared with alkylator-based combination therapy, but without a survival benefit by 5-6 years of follow up.
Topics: Alkylating Agents; Antineoplastic Agents; Clinical Trials as Topic; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; MEDLINE; Neutrophils; Risk; Time Factors; Treatment Outcome; Vidarabine
PubMed: 15512812
DOI: 10.1080/10428190412331283260 -
Cancer Treatment Reviews Dec 2012Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several therapy options are available for symptomatic, treatment-naïve chronic lymphocytic leukemia (CLL). Many of these therapies have been compared against chlorambucil, but have not been directly compared against each other. There is currently no agreed upon standard therapeutic regimen for treatment-naïve CLL.
METHODS
We performed a systematic literature review to identify randomized controlled trials (RCTs) published prior to November 2011 of therapies for previously untreated CLL. We conducted a network meta-analysis using fixed and random effect statistical models to estimate differences between shape and scale parameters of progression-free survival (PFS) curves for each competing therapy. We used the parameter estimates and a Weibull distribution to project mean PFS for each therapy option.
RESULTS
Five RCTs were included in our comparison network. Overall, patients were younger (59-65 years), had good performance status based on the Eastern Cooperative Oncology Group scale (ECOG 0-1), and earlier stage disease (Rai 0-II or Binet A or B). The combination regimen fludarabine with cyclophosphamide and rituximab (FCR) was estimated to yield mean PFS of 76 months (95% CrI: 60, 91), FC 60 months (46, 73), fludarabine 38 months (27, 49), alemtuzumab 24 months (15, 32), and chlorambucil 23 months (15, 32).
CONCLUSION
Our results suggest that FCR has relatively higher potential of preventing disease progression in younger, healthier, treatment-naïve CLL patients and should be considered an optimal initial treatment strategy for this patient population. However, because estimates are based on model simulation, additional studies of FCR are necessary to clinically validate its therapeutic potential.
Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Randomized Controlled Trials as Topic; Rituximab; Vidarabine
PubMed: 22405931
DOI: 10.1016/j.ctrv.2012.02.006 -
The Cochrane Database of Systematic... 2001Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of antiviral pharmacology and of herpes simplex virus eye... (Review)
Review
BACKGROUND
Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of antiviral pharmacology and of herpes simplex virus eye disease have evaluated different commercially available agents, but a systematic review of all comparative clinical studies has not previously been undertaken.
OBJECTIVES
The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis.
SEARCH STRATEGY
Sources searched for relevant studies were the Cochrane Eyes and Vision Group specialized register, The Cochrane Controlled Trials Register - CENTRAL, MEDLINE, EMBASE, Index Medicus, Excerpta Medica Ophthalmology, reference lists of primary reports, review articles, and corneal textbooks and conference proceedings pertaining to ocular virology.
SELECTION CRITERIA
This review includes comparative clinical trials that assessed oral or topical ophthalmic antiviral agents, or physical or chemical debridement in people with active epithelial keratitis.
DATA COLLECTION AND ANALYSIS
The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment.
MAIN RESULTS
This review includes data from 96 trials which randomised a total of 4991 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical and physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, and was useful with debridement.
REVIEWER'S CONCLUSIONS
Currently available and investigational antiviral agents are effective and nearly equivalent, but the combination of an antiviral nucleoside and interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome and should consider the effect of lesion size and other characteristics on treatment response.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Debridement; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 11279774
DOI: 10.1002/14651858.CD002898 -
Leukemia & Lymphoma Mar 2009Rituximab maintenance therapy has emerged as an effective treatment for low-grade lymphomas. No major acute or cumulative toxicities were observed in patients receiving... (Meta-Analysis)
Meta-Analysis Review
Rituximab maintenance therapy has emerged as an effective treatment for low-grade lymphomas. No major acute or cumulative toxicities were observed in patients receiving rituximab maintenance therapy compared with observation arms in clinical trials. However, B-cells are completely depleted throughout the maintenance period and even longer, which may render patients at high risk for infections. Several infections related to rituximab have been reported in the literature. Yet it is not clear whether rituximab maintenance therapy increases the infectious complications or not. To further investigate this topic, we have performed a systematic review and meta-analysis of randomised controlled trials (RCT). The meta-analysis of five RCTs showed that rituximab maintenance therapy significantly increased the relative risk of both infection and neutropenia in patients with lymphoma. On the basis of the available evidence, patients who received rituximab maintenance treatment have higher risk of neutropenia and infection than those who did not. Previously treated patients particularly with fludarabine containing regimens are more susceptible to infectious complications and require extended vigilance.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Humans; Lymphoma; Neutropenia; Opportunistic Infections; Randomized Controlled Trials as Topic; Rituximab; Vidarabine
PubMed: 19263297
DOI: 10.1080/10428190902730219 -
The Cochrane Database of Systematic... Jul 2009Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae.
OBJECTIVES
To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression.
SEARCH STRATEGY
Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included.
DATA COLLECTION AND ANALYSIS
Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI).
MAIN RESULTS
Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period.
AUTHORS' CONCLUSIONS
There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.
Topics: Acyclovir; Antiviral Agents; Developmental Disabilities; Disease Progression; Herpes Simplex; Humans; Infant, Newborn; Randomized Controlled Trials as Topic; Vidarabine
PubMed: 19588350
DOI: 10.1002/14651858.CD004206.pub2 -
The Cochrane Database of Systematic... 2003Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus... (Review)
Review
BACKGROUND
Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken.
OBJECTIVES
The objective of this review is to compare the effects of various treatments for dendritic or geographic herpes simplex virus epithelial keratitis.
SEARCH STRATEGY
Sources searched for relevant studies were the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group trials register), (Issue 3 2002), MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), LILACS (up to 2002), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology.
SELECTION CRITERIA
This review includes comparative clinical trials that assessed one-week and/or two-week healing rates of topical ophthalmic or oral antiviral agents and/or physical or chemical debridement in people with active epithelial keratitis.
DATA COLLECTION AND ANALYSIS
The reviewer extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrollment.
MAIN RESULTS
This review includes data from 97 trials that randomised a total of 5102 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir generally resulted in a significantly greater proportion of participants healing within one week of treatment. Among these three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis, but not better than other antiviral agents, although interferon was very useful combined with debridement or with another antiviral agent such as trifluridine.
REVIEWER'S CONCLUSIONS
Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of herpes simplex virus epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 12917935
DOI: 10.1002/14651858.CD002898 -
The Cochrane Database of Systematic... Dec 2010Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eye disease due to herpes simplex virus (HSV) commonly presents as epithelial keratitis.
OBJECTIVES
To compare the relative effectiveness of antiviral agents, interferon, and corneal débridement in the treatment of acute HSV epithelial keratitis.
SEARCH STRATEGY
We searched CENTRAL (The Cochrane Library 2010, Issue 4), MEDLINE (January 1950 to October 2010), EMBASE (January 1980 to October 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2010), Zetoc (British Library's Electronic Table of Contents), System for Information on Grey Literature in Europe (openSIGLE), Biosciences Information Service (BIOSIS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), Japan Information Center of Science and Technology (JICST-EPlus), and China Academic Journals database (CAJ) via China National Knowledge Infrastructure (CNKI) with citations confirmed using China/Asia On Demand (COAD). There were no language or date restrictions in the search for trials. All databases except CNKI and COAD were last searched on 27 October 2010, CNKI and COAD were searched on 1 April 2010. We also searched literature digests, conference proceedings and reference lists.
SELECTION CRITERIA
Of 152 eligible studies,106 comparative treatment trials involving 5872 eyes with dendritic or geographic epithelial keratitis were analysed for corneal healing over two weeks.
DATA COLLECTION AND ANALYSIS
Interventions were compared at 14 days after trial enrolment by calculating a risk ratio (RR) that was adjusted with indirect RR, assessed by an inconsistency index (I(2) ) and supplemented by a seven-day RR and a hazard ratio (HR).
MAIN RESULTS
Idoxuridine, though uncertainly better in healing outcome than control because of few trials with 14-day follow up, allowed earlier corneal re-epithelialisation. Vidarabine resulted in a significantly better outcome than placebo in one trial (RR 1.96; 95% CI 1.10 to 3.49). Compared to idoxuridine, in combined direct and indirect analyses, vidarabine (RR 1.11; 95% CI 1.03 to 1.19), trifluridine (RR 1.31; 95% CI 1.20 to 1.42), acyclovir (RR 1.23; 95% CI 1.16 to 1.31), brivudine (RR 1.38; 95% CI 1.18 to 1.61), and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) were significantly more effective. Trifluridine (RR 1.12; 95% CI 1.04 to 1.21) and acyclovir (RR 1.11; 95% CI 1.05 to 1.19) appeared more effective than vidarabine. No significant differences were found in comparisons between acyclovir, trifluridine and brivudine. The comparison of ganciclovir to acyclovir was limited by heterogeneity and possible publication bias. The joint use of two topical antivirals (RR 1.00; 95% CI 0.89 to 1.12) and the use of oral acyclovir alone (RR 0.92; 95% CI 0.79 to 1.07) or combined with a topical antiviral (RR 1.08; 95% CI 0.99 to 1.17) appeared as effective as topical antiviral therapy. Compared to antiviral monotherapy, the combination of an antiviral with interferon (RR 1.03; 95% CI 0.99 to 1.07) or with débridement (RR 1.04; 95% CI 0.95 to 1.14) did not yield significantly better outcomes but may have accelerated healing. The corneal epithelial healing outcome was improved when antiviral therapy was added to débridement (RR 1.21; 95% CI 1.04 to 1.42).
AUTHORS' CONCLUSIONS
Trifluridine and acyclovir are more effective than idoxuridine or vidarabine, and similar in therapeutic effectiveness. Brivudine and ganciclovir are at least as effective as acyclovir. While not improving outcome, the combination of interferon and an antiviral agent may speed healing. The effectiveness of corneal epithelial débridement is improved by an antiviral agent.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Interferons; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 21154352
DOI: 10.1002/14651858.CD002898.pub4 -
The Cochrane Database of Systematic... Jan 2007Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus... (Review)
Review
BACKGROUND
Many clinical trials have been performed on the acute treatment of dendritic epithelial keratitis. Surveys of ocular antiviral pharmacology and of herpes simplex virus (HSV) eye disease have evaluated different interventions, but a systematic review of all comparative clinical studies has not previously been undertaken.
OBJECTIVES
The objective of this review was to compare the effects of various therapeutic interventions for dendritic or geographic HSV epithelial keratitis.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library (Issue 3, 2006), MEDLINE (1966 to July 2006, week 3), EMBASE (1980 to 2006, week 30), LILACS (up to August 2006), SIGLE (1980 to March 2005), ZETOC (1 August 2006), BIOSIS (up to 2005), JICT-EPlus (up to 2005), Index Medicus (1960 to 1965), Excerpta Medica Ophthalmology (1960 to 1973), reference lists of primary reports and review articles, and conference proceedings pertaining to ocular virology.
SELECTION CRITERIA
This review included comparative clinical trials that assessed one-week or two-week healing rates of topical ophthalmic or oral antiviral agents and or physical or chemical debridement in people with active epithelial keratitis.
DATA COLLECTION AND ANALYSIS
The review author extracted data and assessed trial quality. Interventions were compared by the proportions of participants healed at seven days and at fourteen days after trial enrolment.
MAIN RESULTS
This review included data from 98 trials that randomised a total of 5211 participants. Compared to idoxuridine, the topical application of vidarabine, trifluridine, or acyclovir resulted in a significantly greater proportion of participants healing within one week of treatment. Among these latter three antiviral agents, no treatment emerged as significantly better for the therapy of dendritic epithelial keratitis. Insufficient placebo-controlled studies were available to assess debridement and other physical or physicochemical methods of treatment. Interferon monotherapy had a slight beneficial effect on dendritic epithelial keratitis but was not better than other antiviral agents. Interferon was very effective when combined with another antiviral agent such as trifluridine.
AUTHORS' CONCLUSIONS
Currently available antiviral agents are effective and nearly equivalent. The combination of a nucleoside antiviral with either debridement or with interferon seems to speed healing. Future trials of the acute treatment of HSV epithelial keratitis must aim to achieve adequate statistical power for assessing the primary outcome of epithelial healing and should consider the effect of lesion size and other characteristics on treatment response.
Topics: Administration, Oral; Administration, Topical; Antiviral Agents; Combined Modality Therapy; Debridement; Humans; Keratitis, Herpetic; Randomized Controlled Trials as Topic
PubMed: 17253484
DOI: 10.1002/14651858.CD002898.pub2 -
The Cochrane Database of Systematic... Feb 2012Chronic lymphocytic leukaemia (CLL) accounts for 25% of all leukaemias and is the most common lymphoid malignancy in Western countries. Standard treatment includes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic lymphocytic leukaemia (CLL) accounts for 25% of all leukaemias and is the most common lymphoid malignancy in Western countries. Standard treatment includes mono- or poly-chemotherapies. Nowadays, monoclonal antibodies are added, especially alemtuzumab and rituximab. However, the impact of these agents remains unclear, as there are hints of an increased risk of severe infections.
OBJECTIVES
To assess alemtuzumab compared with no further therapy, or with other anti-leukaemic therapy in patients with CLL.
SEARCH METHODS
We searched CENTRAL and MEDLINE (from January 1985 to November 2011), and EMBASE (from 1990 to 2009) as well as conference proceedings for randomised controlled trials (RCTs). Two review authors (KB, NS) independently screened search results.
SELECTION CRITERIA
We included RCTs comparing alemtuzumab with no further therapy or comparing alemtuzumab with anti-leukaemic therapy such as chemotherapy or monoclonal antibodies in patients with histologically-confirmed B-cell CLL. Both pretreated and chemotherapy-naive patients were included.
DATA COLLECTION AND ANALYSIS
We used hazard ratios (HR) as an effect measure for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for response rates, treatment-related mortality (TRM) and adverse events. Two review authors independently extracted data and assessed the quality of trials.
MAIN RESULTS
Our search strategies led to 1542 potentially relevant references. Of these, we included five RCTs involving 845 patients. Overall, we judged the quality of the five trials as moderate. All trials were reported as randomised and open-label studies. However, two trials were published as abstracts only, therefore, we were unable to assess the potential risk of bias for these trials in detail. Because of the small number of studies in each analysis (two), the quantification of heterogeneity was not reliable.Two trials (N = 356) assessed the efficacy of alemtuzumab compared with no further therapy. One trial (N = 335), reported a statistically significant OS advantage for all patients receiving alemtuzumab (HR 0.65 (95% confidence interval (CI) 0.45 to 0.94; P = 0.021). However, no improvement was seen for the subgroup of patients in Rai stage I or II (HR 1.07; 95% CI 0.62 to 1.84; P = 0.82). In both trials, the complete response rate (CRR) (RR 2.61; 95% CI 1.26 to 5.42; P = 0.01) and PFS (HR 0.58; 95% CI 0.44 to 0.76; P < 0.0001) were statistically significantly increased under therapy with alemtuzumab. The potential heterogeneity seen in the forest plot could be due to the different study designs: One trial evaluated alemtuzumab additional to fludarabine as relapse therapy; the other trial examined alemtuzumab compared with no further therapy for consolidation after first remission.There was no statistically significant difference for TRM between both arms (RR 0.57; 95% CI 0.17 to 1.90; P = 0.36). A statistically significant higher rate of CMV reactivation (RR 10.52; 95% CI 1.42 to 77.68; P = 0.02) and infections (RR 1.32; 95% CI 1.01 to 1.74; P = 0.04) occurred in patients receiving alemtuzumab. Seven severe infections (64%) in the alemtuzumab arm in the GCLLSG CLL4B study led to premature closure.Two trials (N = 177), evaluated alemtuzumab versus rituximab. Neither study reported OS or PFS. We could not detect a statistically significant difference for CRR (RR 0.85; 95% CI 0.67 to 1.08; P = 0.18) or TRM (RR 3.20; 95% CI 0.66 to 15.50; P = 0.15) between both arms. However, the CLL2007FMP trial was stopped early due to an increase in mortality in the alemtuzumab arm. More serious adverse events occurred in this arm (43% versus 22% (rituximab), P = 0.006).One trial (N = 297), assessed the efficacy of alemtuzumab compared with chemotherapy (chlorambucil). For this trial, no HR is reported for OS. Median survival has not yet been reached, 84% of patients were alive in each arm at the data cut-off or at the last follow-up date (24.6 months). The TRM between arms shows no statistical significant difference (0.6% versus 2.0%; P = 0.34). Alemtuzumab statistically significantly improves PFS (HR 0.58; 95% CI 0.43 to 0.77; P = 0.0001), time to next treatment (23.3 compared with 14.7 months; P = 0.0001), ORR (83.2% versus 55.4%; P < 0.0001), CRR (24.2% versus 2.0%; P < 0.0001), and minimal residual disease rate (7.4% versus 0%; P = 0.0008) compared with chlorambucil. Statistically, significantly more asymptomatic (51.7% versus 7.4%) and symptomatic cytomegalovirus (CMV) infections (15.4% versus 0%) occurred in the patients treated with alemtuzumab.
AUTHORS' CONCLUSIONS
In summary, the currently available evidence suggests an OS, CRR and PFS benefit for alemtuzumab compared with no further therapy, but an increased risk for infections in general, CMV infections and CMV reactivations. The role of alemtuzumab versus rituximab still remains unclear, further trials with longer follow-up and overall survival as primary endpoint are needed to evaluate the effects of both agents compared with each other. Alemtuzumab compared with chlorambucil seems to be favourable in terms of PFS, but a longer follow-up period and trials with overall survival as primary endpoint are needed to determine whether this effect will translate into a survival advantage.
Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Chlorambucil; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Randomized Controlled Trials as Topic; Rituximab; Vidarabine
PubMed: 22336834
DOI: 10.1002/14651858.CD008078.pub2 -
The Cochrane Database of Systematic... Apr 2011Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.
OBJECTIVES
To evaluate the benefits and harms of phyllanthus species for patients with chronic HBV infection.
SEARCH STRATEGY
Searches were performed in The Cochrane Hepato-Biliary Gorup Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and the Chinese Biomedical CD Database, China Network Knowledge Information, Chinese Science Journal Database, TCM Online, and Wanfang Database. Conference proceedings in Chinese were handsearched. All searches were conducted until October 2010.
SELECTION CRITERIA
Randomised clinical trials comparing phyllanthus species with placebo or no intervention for patients with chronic HBV infection. Co-interventions were allowed if all comparison groups had received the same co-interventions. We included trials irrespective of blinding, publication status, or language.
DATA COLLECTION AND ANALYSIS
Two authors selected the trials and extracted the data independently. The RevMan software was used for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CI). Risk of bias was assessed to control for systematic errors. Trial sequential analysis was used in order to control for random errors.
MAIN RESULTS
A total of 16 randomised trials with 1326 patients were included. One trial with 42 participants compared phyllanthus with placebo. The trial found no significant difference in HBeAg seroconversion after the end of treatment (RR 0.9; 95% CI 0.73 to 1.25) or follow-up (RR 1.00; 95% CI 0.63 to 1.60). No other outcomes could be assessed. Fifteen trials compared phyllanthus plus an antiviral drug like interferon alpha, lamivudine, adefovir dipivoxil, thymosin, vidarabine, or conventional treatment with the same antiviral drug alone. Phyllanthus did significantly affect serum HBV DNA (RR 0.69; 95% CI 0.52 to 0.91, P = 0.008; I(2) = 71%), serum HBeAg (RR 0.70; 95% CI 0.60 to 0.81, P < 0.00001; I(2) = 68%), and HBeAg seroconversion (RR 0.77; 95% CI 0.63 to 0.92, P = 0.005; I(2) = 78%), but the heterogeneity was substantial. The result obtained regarding serum HBV DNA was not supported by trial sequential analysis. None of the trials reported mortality and hepatitis B-related morbidity, quality of life, or liver histology. Only two trials reported adverse events with numbers without significant differences. No serious adverse events were reported.
AUTHORS' CONCLUSIONS
There is no convincing evidence that phyllanthus compared with placebo benefits patients with chronic HBV infection. Phyllanthus plus an antiviral drug may be better than the same antiviral drug alone. However, heterogeneity, systematic errors, and random errors question the validity of the results. Clinical trials with large sample size and low risk of bias are needed to confirm our findings. Species of phyllanthus should be reported in future trials, and a dose-finding design is warranted.
Topics: Antiviral Agents; DNA, Viral; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Phyllanthus; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic
PubMed: 21491412
DOI: 10.1002/14651858.CD008960.pub2