Abstract:
BACKGROUND:The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. MATERIALS AND METHODS:We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. RESULTS:A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95% CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). CONCLUSIONS:Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Qi WX,Shen Z,Tang LN,Yao Ydoi
10.1007/s00228-014-1687-9subject
Has Abstractpub_date
2014-08-01 00:00:00pages
893-906issue
8eissn
0031-6970issn
1432-1041journal_volume
70pub_type
杂志文章,meta分析abstract:PURPOSE:The aim of this study was to evaluate the population pharmacokinetics (PK) and exposure-response relationship of edoxaban in patients with non-valvular atrial fibrillation (AF). METHODS:Concentration data from 1,134 subjects in 11 clinical studies (eight phase I, one phase II, and two phase III) were used to p...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-014-1736-4
更新日期:2014-11-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the association between polypharmacy with health-related quality of life (HRQoL) and medication regimen complexity with HRQoL in residential aged care facilities (RACFs). METHODS:A cross-sectional study of 383 residents from six Australian RACFs was conducted. The pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2075-4
更新日期:2016-09-01 00:00:00
abstract::Caffeine metabolites in urine from premature infants were analysed by TLC and HPLC. Caffeine, dimethyluric acids, mono- and dimethylxanthines and, for the first time, a uracil derivative (6-amino-5-[N-methylformylamino]-1,3-dimethyluracil) were identified. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613531
更新日期:1986-01-01 00:00:00
abstract::Atropine-induced bradycardia is traditionally ascribed to central vagal stimulation, although bradycardia has also been observed after administration of quarternary amines. Pirezepine, a selective M1-antagonist, causes bradycardia in therapeutic doses for which a peripheral mechanism is postulated. This hypothesis has...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558245
更新日期:1988-01-01 00:00:00
abstract::The gastric inhibitory effects of CM57755, a new histamine H2 receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimet...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614192
更新日期:1986-01-01 00:00:00
abstract::The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 2...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314864
更新日期:1992-01-01 00:00:00
abstract::Blood levels of racemic chloroquine and its main metabolites desethylchloroquine and bisdesethylchloroquine were measured in 29 patients treated chronically for rheumatoid arthritis. In six patients, the concentrations were followed during a one day dosage interval. There was considerable intersubject variability in t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00280130
更新日期:1992-01-01 00:00:00
abstract::We have studied the antiaggregatory effect of fenflumizole, a new non-steroidal antiinflammatory imidazole derivative, in ten patients with unstable angina pectoris. We have measured the aggregation induced by arachidonic acid (AA), ADP, and collagen, and serum or plasma concentrations of beta-thromboglobulin (beta-TG...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00606628
更新日期:1987-01-01 00:00:00
abstract:OBJECTIVE:We investigated the effects of treatment with Saint John's wort (hypericum perforatum) extract on the urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol in order to assess the effect of this extract on the activity of hepatic xenobiotic metabolizing enzymes. METHODS:Forty-eight he...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-002-0527-5
更新日期:2002-12-01 00:00:00
abstract:OBJECTIVE:The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. RESULTS:Both oral and intramuscular artemether were well-tol...
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/s002280050295
更新日期:1997-01-01 00:00:00
abstract::Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00607953
更新日期:1986-01-01 00:00:00
abstract::The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614557
更新日期:1988-01-01 00:00:00
abstract::The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous...
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/BF00637630
更新日期:1987-01-01 00:00:00
abstract::A series of elegant experimental studies and careful clinical observation over a decade or more have led to the concept of 'infarct expansion' and 'remodelling' of the heart, culminating in a number of major mortality studies indicating the effectiveness of angiotensin-converting enzyme (ACE) inhibitors in patients af...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1996-01-01 00:00:00
abstract:OBJECTIVE:The aim was to develop a model to describe the population pharmacokinetics of nevirapine in South African human immunodeficiency virus (HIV)-infected patients who were taking nevirapine-based antiretroviral therapy concomitantly or in the absence of rifampicin-based tuberculosis therapy. METHODS:Patients wer...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-008-0481-y
更新日期:2009-01-01 00:00:00
abstract::We have compared the effect on ventilation of ketorolac, an injectable non-steroidal analgesic, with that of morphine in a randomized, double-blind, cross-over study, using two doses of ketorolac (10 and 90 mg i.m.) and one of morphine (10 mg i.m.). The effect on ventilation was measured with a CO2 rebreathing techniq...
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/BF00558243
更新日期:1988-01-01 00:00:00
abstract::Thirty patients suffering from essential hypertension were treated successively with placebo, hydralazine alone, and pindolol (Visken) combined with hydralazine. Hydralazine caused a statistically significant reduction in blood pressure and an increase in pulse rate as compared with the placebo: palpitations were an i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614002
更新日期:1975-12-19 00:00:00
abstract:OBJECTIVE:To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS:Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Ren...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050504
更新日期:1998-09-01 00:00:00
abstract:PURPOSE:The use of melatonin is increasing among Swedish children and adolescents despite deficient knowledge of usage in these groups. The aim of this study was to investigate the use of melatonin in Swedish children and adolescents according to age, gender, dosage, treatment duration, and use of attention deficit hyp...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1866-3
更新日期:2015-07-01 00:00:00
abstract:PURPOSE:The study aimed to test the hypothesis that hospital electronic prescribing and medicine administration system (HEPMA) implementation impacted patient discharge letter quality, nature and frequency of prescribing errors. METHOD:A quasi experimental before and after retrospective case note review was conducted ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-017-2274-7
更新日期:2017-10-01 00:00:00
abstract::The pharmacokinetics and bioavailability of digitoxin were examined in six normal human subjects using an assay that separates digitoxin from its metabolites. After intravenous administration, the mean systemic clearance was 2.44 ml/min; the volume of distribution was 0.47 l/kg; and the elimination half-life was 6.5 d...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the association between migration status and education level and the use of recommended drugs after first acute myocardial infarction (MI). METHODS:A nationwide cohort study performed in Sweden from January 1, 2006 to August 1, 2008. The cohort consisted of 49,037 in...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1821-3
更新日期:2015-04-01 00:00:00
abstract::In a double-blind, placebo-controlled cross-over study, the plasma atrial natriuretic peptide (ANP) levels of nine young and ten elderly hypertensive patients were compared after placebo and after treatment with 120 mg verapamil given three times daily over 4 weeks. During placebo, plasma ANP levels proved to be highe...
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/BF01409206
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:To develop quality prescribing indicators for general practitioners (GPs) who are non-monitored and not included in pay-for-performance programs, and to determine compliance with incentivized and non-incentivized indicators. STUDY DESIGN:Descriptive cross sectional study. SETTING:Aljarafe Primary Health Car...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1542-4
更新日期:2013-10-01 00:00:00
abstract::Accidental intoxication with tramadol of a 6-month old infant was followed by severe cerebral depression. Studies on serum, cerebrospinal fluid, and urine drug levels indicated complete penetration of the blood-cerebrospinal fluid barrier by tramadol. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543498
更新日期:1984-01-01 00:00:00
abstract::Thirty-eight severely hypertensive patients were treated with oral clonidine. Each patient received a "loading" dose of 0.2 mg clonidine, followed by 0.1 mg hourly until the blood pressure was substantially reduced, or until a total dose of 0.8 mg has been administered. Thirty-five (82.1%) patients responded favourabl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00606664
更新日期:1986-01-01 00:00:00
abstract::Information must be collected, evaluated and utilized to support every qualified activity. Medicine, with a written scientific tradition stretching back more than 2,000 years, is no exception. Here, we discuss a number of important items associated with the establishment of a drug information centre run by clinical ph...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1484-x
更新日期:2013-05-01 00:00:00
abstract::The effect of menstrual cycle on the pharmacokinetics of theophylline has been studied in 9 female asthmatic patients. At three different times during the cycle (first, tenth and twentieth days) each subject received an i.v. infusion of 240 mg theophylline. Significant changes were found in the kinetics of theophyllin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02657059
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:To assess relative roles of the intestinal and hepatic stereoselective metabolism of nicardipine in an oral first-pass disposal with and without grapefruit juice intake. METHODS:The kinetic profiles of (+)- and (-)-nicardipine were studied in the six normal healthy male volunteers who received oral (40 mg) ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280000235
更新日期:2000-12-01 00:00:00
abstract:OBJECTIVE:To assess the effect of an intervention on general practitioners' (GPs) knowledge about the diagnosis and treatment of asthma, including the prescribing of anti-asthmatic drugs, and asthmatic patients' knowledge about their disease. METHODS:The study took place in the south-west region of Stockholm County. I...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050361
更新日期:1997-01-01 00:00:00