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Annals of Surgical Oncology Dec 2016FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it... (Review)
Review
BACKGROUND
FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC.
METHODS
The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate.
RESULTS
Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity.
CONCLUSIONS
Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.
Topics: Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Pancreatectomy; Pancreatic Neoplasms; Radiotherapy; Radiotherapy, Adjuvant; Survival Rate
PubMed: 27370653
DOI: 10.1245/s10434-016-5373-2 -
The Cochrane Database of Systematic... Jul 2016Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years.
OBJECTIVES
To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia.
SEARCH METHODS
We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics.
DATA COLLECTION AND ANALYSIS
Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence.
MAIN RESULTS
Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness.
AUTHORS' CONCLUSIONS
Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.
Topics: Administration, Oral; Amisulpride; Antipsychotic Agents; Benzodiazepines; Fluphenazine; Humans; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride; Treatment Outcome
PubMed: 27370402
DOI: 10.1002/14651858.CD010832.pub2 -
PloS One 2016In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/OBJECTIVES
In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET.
METHODS
Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling.
RESULTS
Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13), or OS (RR 1.03; CI 0.77-1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04-1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82) and lower overall renal toxicity (RR 3.61; CI 1.24-10.51).
CONCLUSION
Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Fluorouracil; Humans; Interferons; Neoplasm Metastasis; Neuroendocrine Tumors; Randomized Controlled Trials as Topic; Somatostatin; Streptozocin; Treatment Outcome
PubMed: 27362760
DOI: 10.1371/journal.pone.0158140 -
Drug Design, Development and Therapy 2016Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence.
METHODS
PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively.
RESULTS
A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%-17.7%), disease control rate was 55.0% (95% CI: 51.5%-58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%-33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease.
CONCLUSION
Our study showed that GemErlo is associated with reasonable activity in treating patients with locally advanced or metastatic pancreatic cancer. Most of the AEs were tolerable, while some severe AEs needed careful detection.
Topics: Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Erlotinib Hydrochloride; Humans; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Gemcitabine
PubMed: 27358556
DOI: 10.2147/DDDT.S105442 -
Clinical Epigenetics 2016Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent... (Comparative Study)
Comparative Study Review
BACKGROUND
Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population.
METHODS
Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS.
RESULTS
Overall survival (OS) rate was 33.2 vs. 21.4 % (RR 0.83, 95 % CI 0.71-0.98) and overall response rate (ORR) 23.7 vs. 13.4 % (RR 0.87, 95 % CI 0.81-0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 % CI 0.64-0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact.
CONCLUSION
Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.
Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; DNA Methylation; Decitabine; Epigenesis, Genetic; Female; Humans; Leukemia, Myeloid, Acute; Male; Myelodysplastic Syndromes; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 27307795
DOI: 10.1186/s13148-016-0233-2 -
Blood Jul 2016
Meta-Analysis Review
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Animals; Atrial Fibrillation; Humans; Incidence; Leukemia; Lymphoma; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines
PubMed: 27247135
DOI: 10.1182/blood-2016-05-712828 -
The Cochrane Database of Systematic... May 2016Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Female pattern hair loss (FPHL), or androgenic alopecia, is the most common type of hair loss affecting women. It is characterised by progressive shortening of the duration of the growth phase of the hair with successive hair cycles, and progressive follicular miniaturisation with conversion of terminal to vellus hair follicles (terminal hairs are thicker and longer, while vellus hairs are soft, fine, and short). The frontal hair line may or may not be preserved. Hair loss can have a serious psychological impact on women.
OBJECTIVES
To determine the efficacy and safety of the available options for the treatment of female pattern hair loss in women.
SEARCH METHODS
We updated our searches of the following databases to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (2015, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1872), AMED (from 1985), LILACS (from 1982), PubMed (from 1947), and Web of Science (from 1945). We also searched five trial registries and checked the reference lists of included and excluded studies.
SELECTION CRITERIA
We included randomised controlled trials that assessed the efficacy of interventions for FPHL in women.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality, extracted data and carried out analyses.
MAIN RESULTS
We included 47 trials, with 5290 participants, of which 25 trials were new to this update. Only five trials were at 'low risk of bias', 26 were at 'unclear risk', and 16 were at 'high risk of bias'.The included trials evaluated a wide range of interventions, and 17 studies evaluated minoxidil. Pooled data from six studies indicated that a greater proportion of participants (157/593) treated with minoxidil (2% and one study with 1%) reported a moderate to marked increase in their hair regrowth when compared with placebo (77/555) (risk ratio (RR) = 1.93, 95% confidence interval (CI) 1.51 to 2.47; moderate quality evidence). These results were confirmed by the investigator-rated assessments in seven studies with 1181 participants (RR 2.35, 95% CI 1.68 to 3.28; moderate quality evidence). Only one study reported on quality of life (QoL) (260 participants), albeit inadequately (low quality evidence). There was an important increase of 13.18 in total hair count per cm² in the minoxidil group compared to the placebo group (95% CI 10.92 to 15.44; low quality evidence) in eight studies (1242 participants). There were 40/407 adverse events in the twice daily minoxidil 2% group versus 28/320 in the placebo group (RR 1.24, 95% CI 0.82 to 1.87; low quality evidence). There was also no statistically significant difference in adverse events between any of the individual concentrations against placebo.Four studies (1006 participants) evaluated minoxidil 2% versus 5%. In one study, 25/57 participants in the minoxidil 2% group experienced moderate to greatly increased hair regrowth versus 22/56 in the 5% group (RR 1.12, 95% CI 0.72 to 1.73). In another study, 209 participants experienced no difference based on a visual analogue scale (P = 0.062; low quality evidence). The assessments of the investigators based on three studies (586 participants) were in agreement with these findings (moderate quality evidence). One study assessed QoL (209 participants) and reported limited data (low quality evidence). Four trials (1006 participants) did not show a difference in number of adverse events between the two concentrations (RR 1.02, 95% CI 0.91 to 1.20; low quality evidence). Both concentrations did not show a difference in increase in total hair count at end of study in three trials with 631 participants (mean difference (MD) -2.12, 95% CI -5.47 to 1.23; low quality evidence).Three studies investigated finasteride 1 mg compared to placebo. In the finasteride group 30/67 participants experienced improvement compared to 33/70 in the placebo group (RR 0.95, 95% CI 0.66 to 1.37; low quality evidence). This was consistent with the investigators' assessments (RR 0.77, 95% CI 0.31 to 1.90; low quality evidence). QoL was not assessed. Only one study addressed adverse events (137 participants) (RR 1.03, 95% CI 0.45 to 2.34; low quality evidence). In two studies (219 participants) there was no clinically meaningful difference in change of hair count, whilst one study (12 participants) favoured finasteride (low quality evidence).Two studies (141 participants) evaluated low-level laser comb therapy compared to a sham device. According to the participants, the low-level laser comb was not more effective than the sham device (RR 1.54, 95% CI 0.96 to 2.49; and RR 1.18, 95% CI 0.74 to 1.89; moderate quality evidence). However, there was a difference in favour of low-level laser comb for change from baseline in hair count (MD 17.40, 95% CI 9.74 to 25.06; and MD 17.60, 95% CI 11.97 to 23.23; low quality evidence). These studies did not assess QoL and did not report adverse events per treatment arm and only in a generic way (low quality evidence). Low-level laser therapy against sham comparisons in two separate studies also showed an increase in total hair count but with limited further data.Single studies addressed the other comparisons and provided limited evidence of either the efficacy or safety of these interventions, or were unlikely to be examined in future trials.
AUTHORS' CONCLUSIONS
Although there was a predominance of included studies at unclear to high risk of bias, there was evidence to support the efficacy and safety of topical minoxidil in the treatment of FPHL (mainly moderate to low quality evidence). Furthermore, there was no difference in effect between the minoxidil 2% and 5% with the quality of evidence rated moderate to low for most outcomes. Finasteride was no more effective than placebo (low quality evidence). There were inconsistent results in the studies that evaluated laser devices (moderate to low quality evidence), but there was an improvement in total hair count measured from baseline.Further randomised controlled trials of other widely-used treatments, such as spironolactone, finasteride (different dosages), dutasteride, cyproterone acetate, and laser-based therapy are needed.
Topics: Alopecia; Drug Administration Schedule; Female; Finasteride; Hair; Humans; Low-Level Light Therapy; Minoxidil; Randomized Controlled Trials as Topic
PubMed: 27225981
DOI: 10.1002/14651858.CD007628.pub4 -
The Lancet. Oncology Jun 201635% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population.
METHODS
We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model.
FINDINGS
We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%).
INTERPRETATION
Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX.
FUNDING
None.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Pancreatic Neoplasms; Prognosis; Survival Rate; Gemcitabine
PubMed: 27160474
DOI: 10.1016/S1470-2045(16)00172-8 -
Advances in Therapy May 2016Renal safety is an important factor in selecting the most appropriate nucleos(t)ide analog (NA) treatment for patients with chronic hepatitis B (CHB). This systematic... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Renal safety is an important factor in selecting the most appropriate nucleos(t)ide analog (NA) treatment for patients with chronic hepatitis B (CHB). This systematic literature review and network meta-analysis aimed to assess renal function associated with telbivudine treatment compared to other NAs in patients with CHB.
METHODS
A systematic literature search via Medline, Medline In-Process, Embase, and the Cochrane library for publications of randomized controlled trials and observational studies was conducted. Network meta-analysis was performed to compare renal function with telbivudine treatment versus other NAs after 1 year of therapy.
RESULTS
Overall, 40 (six randomized controlled and 34 observational) studies were included for review. Telbivudine consistently showed an improvement in renal function as measured by an estimated glomerular filtration rate (eGFR) over various time points regardless of the method of measurement. Changes in eGFR (mL/min) from baseline and corresponding 95% credible intervals with various NAs were as follows: monotherapies (telbivudine: 7.78 [6.91, 8.65], entecavir: -1.07 [-4.80, 2.62], lamivudine: -6.08 [-13.35, 1.15], tenofovir: -9.53 [-14.31, -4.89]) and combination therapies (telbivudine + adefovir: 8.37 [-34.00, 50.34], telbivudine + tenofovir: 8.29 [-0.05, 16.64], entecavir + adefovir: 4.15 [-38.55, 46.37], telbivudine + lamivudine: 0.51 [-11.77, 12.96], and lamivudine + adefovir: -0.39 [-42.48, 41.21]). At 1 year, the change in eGFR from baseline was significantly higher with telbivudine compared to other NAs.
CONCLUSION
The systematic literature review and network meta-analysis provide evidence that telbivudine is associated with significant improvement in renal function in patients with CHB, either alone or in combination with other NAs.
FUNDING
Novartis Pharma AG.
Topics: Antiviral Agents; Glomerular Filtration Rate; Hepatitis B, Chronic; Humans; Kidney; Protective Agents; Telbivudine; Thymidine
PubMed: 27146675
DOI: 10.1007/s12325-016-0337-2 -
Oncotarget May 2016Currently, no consensus exists regarding the optimal oral prophylactic regimens for hepatitis B surface antigen seropositive patients undergoing chemotherapy. We aimed... (Comparative Study)
Comparative Study Meta-Analysis Review
Systematic review with network meta-analysis: Comparative efficacy of oral nucleos(t)ide analogues for the prevention of chemotherapy-induced hepatitis B virus reactivation.
OBJECTIVES
Currently, no consensus exists regarding the optimal oral prophylactic regimens for hepatitis B surface antigen seropositive patients undergoing chemotherapy. We aimed to compare the efficacy of oral nucleos(t)ide analogues (NAs), including lamivudine, entecavir, adefovir, telbivudine and tenofovir, for the prevention of chemotherapy-induced hepatitis B virus (HBV) reactivation and its related morbidity and mortality in patients with chronic HBV (CHB) infection.
RESULTS
Fifty-two eligible articles consisting of 3892 participants were included. For HBV reactivation, prophylactic treatment with NAs were all significantly superior to no prophylaxis, with odds ratio (OR) from 0.00 (95% confidence interval [CI] 0.00~0.04) for the most effective intervention (tenofovir) to 0.10 (95% CI 0.06~0.14) for the least effective intervention (lamivudine). For secondary outcomes, prophylaxis with NAs also significantly outperformed observation. The results suggested that entecavir reduced the risk of HBV related hepatitis (predicted probability, 83%), HBV related death (68%) and all causes of hepatitis (97%) most efficaciously. It ranked second in decreasing all causes of death (34%).
MATERIALS AND METHODS
PubMed, Embase and Cochrane Library database were searched for controlled trials up to March 31, 2015. Primary outcome was the incidence of HBV reactivation. Secondary outcomes included the incidence of HBV-related hepatitis and death, all causes of hepatitis and death. Network meta-analysis combined direct and indirect evidence to estimate ORs for the clinical outcomes. A mean ranking and the probability of optimal therapeutic regime was obtained for each treatment based on clinical outcomes.
CONCLUSIONS
Available evidence suggests that prophylatic therapy with tenofovir and entecavir may be the most potent interventions in prevention of HBV reactivation and HBV-related morbidity and mortality for CHB infection patients undergoing chemotherapy.
Topics: Adenine; Antineoplastic Agents; Antiviral Agents; Controlled Clinical Trials as Topic; Guanine; Hepatitis B; Hepatitis B virus; Host-Pathogen Interactions; Humans; Lamivudine; Organophosphonates; Telbivudine; Thymidine; Virus Activation
PubMed: 27121321
DOI: 10.18632/oncotarget.8907