Abstract：
PURPOSE:Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. METHODS:We searched databases such as PubMed and Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings for records up to August 2013 to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95 % confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of included studies. RESULTS:A total of 3,060 patients with a variety of solid tumors from ten clinical trials were included in our analysis. The overall incidence of FAEs associated with aflibercept was 5.1 % (95%CI: 3.8-6.8 %). The use of aflibercept significantly increased the risk of FAEs compared to patients treated with control medication (OR 1.81, 95 % CI: 1.20-2.72, p = 0.004). Additionally, the most common causes of FAEs were infection (38.8 %), hemorrhage (5.9 %) and GI perforation (5.9 %), respectively. CONCLUSIONS:With available evidence, the use of aflibercept is associated with an increased risk of FAEs compared to controls. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept remains justified in its approved indications.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Qi WX,Tang LN,Shen Z,Yao Ydoi
10.1007/s00228-013-1633-2subject
Has Abstractpub_date
2014-04-01 00:00:00pages
461-7issue
4eissn
0031-6970issn
1432-1041journal_volume
70pub_type
杂志文章,meta分析abstract：PURPOSE:To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC(OPZ)) to its metabolites 5-hydroxyomeprazole (AUC(5OH)) and omeprazole sulfone (AUC(SUL)) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. METHODS:Data were obtained f...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-011-1136-y
更新日期：2012-04-01 00:00:00
abstract：OBJECTIVE:To compare the efficacy of activated charcoal and gastric lavage in preventing the absorption of moclobemide, temazepam, and verapamil 30 min after drug ingestion. METHODS:In this randomized cross-over study with three phases, nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg t...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280000139
更新日期：2000-07-01 00:00:00
abstract：CONTEXT:Adverse drug reactions (ADRs) are responsible for 5 % of hospital admissions, but hospital re-admission induced by ADRs remains poorly documented. OBJECTIVE:The aim of this study was to estimate the rate of hospital re-admission and the factors associated with re-admission in the patients over the age of 65 ye...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2022-4
更新日期：2016-05-01 00:00:00
abstract：PURPOSE:To quantify pharmacokinetic (PK) and pharmacodynamic (PD) relationships of various classes of GABAA agonists in healthy volunteers, in order to investigate the sensitivity of the biomarker responses due to differing GABAA-subtype selectivity and to explore the correlation between biomarker responses and side ef...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1007/s00228-015-1918-8
更新日期：2015-10-01 00:00:00
abstract：:Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most promin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563100
更新日期：1979-04-17 00:00:00
abstract：:To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were mea...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198297
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVE:The efficacy, safety, tolerability and speed of onset of the hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg) and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe hypertension (Diastolic BP > or = 115 mmHg). PATIENTS:The ages of the patients ranged from...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050158
更新日期：1996-01-01 00:00:00
abstract：:The metabolic fate and ACTH-suppressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618778
更新日期：1981-01-01 00:00:00
abstract：OBJECTIVE:To investigate whether an association between the use of selective serotonin reuptake inhibitor (SSRI) antidepressants and abnormal bleeding is demonstrated in a large population study. METHODS:An observational cohort study using cohorts from the Drug Safety Research Unit's prescription event monitoring data...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100263
更新日期：2001-05-01 00:00:00
abstract：AIM:It has been reported that verapamil and atorvastatin are inhibitors of both P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A4, and verapamil is a substrate of both P-gp and CYP3A4. Thus, it could be expected that atorvastatin would alter the absorption and metabolism of verapamil. METHODS:The pharmaco...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-007-0447-5
更新日期：2008-05-01 00:00:00
abstract：:The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective beta-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) beta-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1-2 hypertensive men. M lowered pulse rate more than P. Sy...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00558292
更新日期：1989-01-01 00:00:00
abstract：PURPOSE:The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). METHODS:Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studie...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2132-z
更新日期：2017-01-01 00:00:00
abstract：:The bioavailability of a new controlled release formulation of indomethacin lysine salt in tablets was tested in 6 healthy humans against a conventional indomethacin lysinate formulation in capsules. Both contained 100 mg of the drug, i.e. 70 mg indomethacin. Peak plasma levels were lower and more lasting and the AUC ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00609963
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice. METHODS:Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02848-6
更新日期：2020-05-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0765-9
更新日期：2004-07-01 00:00:00
abstract：OBJECTIVE:To investigate the usefulness of the 3-hydroxylation of quinine as a biomarker reaction for the activity of CYP3A4 in man and to study the interindividual variation in the metabolic ratio (MR), i.e. quinine/3-hydroxyquinine. METHODS:Data from a previous study (A) was used for determination of the MR of quini...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s00228-003-0575-5
更新日期：2003-05-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the influence of patient characteristics such as age and stroke and bleeding risks on decisions for antithrombotic treatment in patients with atrial fibrillation (AF). METHODS:This was a retrospective, population-based study including AF patients initiated with eith...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2289-0
更新日期：2017-10-01 00:00:00
abstract：AIMS:The goal of this study was to analyze persistence and the treatment-free interval in patients being prescribed biological drugs in rheumatology practices in Germany. METHODS:Patients who received a first prescription of biological drugs between 2008 and 2016 in 21 rheumatologists in Germany were included in this ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-019-02627-y
更新日期：2019-05-01 00:00:00
abstract：:Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314953
更新日期：1991-01-01 00:00:00
abstract：:We have assessed the effect of omeprazole on various endocrine functions in man. Eight healthy subjects took 60 mg omeprazole or placebo daily for 1 week in a double-blind, randomized, cross-over study. On Day 7 basal concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin, testostero...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00543980
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:To investigate the characteristics of ADRs in patients admitting at the emergency room of a tertiary hospital. METHODS:We collected the patient records of 1600 emergency room visits of a university hospital in 2018. The patient files were studied retrospectively and all possible ADRs were identified and regist...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03043-3
更新日期：2020-11-13 00:00:00
abstract：:Pharmacokinetic and metabolic studies with 3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of 3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicate...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00614015
更新日期：1975-12-19 00:00:00
abstract：:The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00568397
更新日期：1981-01-01 00:00:00
abstract：:In 6 normal volunteers given single oral doses of 250,500 and 1000 mg ticlopidine (T), the peak plasma level of unchanged drug was reached after about 2 h. There was no correlation between the plasma T level and its inhibitory effect on platelet function, expressed as % inhibition of ADP-induced aggregation. By means ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00626364
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:Adverse drug events (ADEs) are harmful and occur with alarming frequency in critically ill patients. Complex pharmacotherapy with multiple medications increases the probability of a drug interaction (DI) and ADEs in patients in intensive care units (ICUs). The objective of the study is to determine the frequenc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0987-y
更新日期：2011-06-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to investigate the influence of clinical and genetic factors on warfarin dose requirements in the Japanese population. METHODS:We enrolled 125 patients on stable warfarin anticoagulant therapy with an international normalized ratio maintained between 1.5 and 3.0. PCR-based methods w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0685-9
更新日期：2009-11-01 00:00:00
abstract：:The biliary excretion of mebendazole has been investigated in two patients to whom it was given for the treatment of echinococcosis, although it was found to be only partly effective. Oral mebendazole was extensively metabolized and the conjugated parent substance and its metabolites were excreted in the bile. One pat...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544020
更新日期：1983-01-01 00:00:00
abstract：PURPOSE:Olaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for ovarian and metastatic breast cancer. Increased serum creatinine levels have been observed in patients taking olaparib, but the underlying mechanism is unknown. This study aimed to investigate if patients receiving olaparib have increased...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03070-0
更新日期：2021-02-01 00:00:00
abstract：:Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 +/- 0.15 mg/day) alone in 13 essen...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00558378
更新日期：1981-01-01 00:00:00
abstract：:Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558149
更新日期：1989-01-01 00:00:00
