Abstract:
PURPOSE:In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the efficacy and safety of novel drugs for advanced melanoma in daily routine practice. METHODS:A retrospective observational study was conducted on all Polish patients (1170 patients), diagnosed with advanced metastatic melanoma, treated with the following drugs: vemurafenib, dabrafenib, and ipilimumab. The antitumor efficacy of these agents was retrospectively assessed by Response Evaluation Criteria in Solid Tumors in the case of BRAF inhibitors and by Immune-Related Response Criteria in the case of ipilimumab therapy. Adverse events were assessed in relation to the morphologic parameters of blood, nephrotoxicity, and hepatotoxicity. RESULTS:The overall response to treatment with BRAF inhibitors (vemurafenib and dabrafenib) was similar with a slightly better outcome in the group treated with vemurafenib. Compared to clinical trials, the objective response rate was slightly worse for both BRAF inhibitors (30% and 42% for dabrafenib and vemurafenib, respectively), as well as the immune-related response for ipilimumab (1%). There was no significant difference in patient's response rates regardless of what lines of treatment (first, second, or next) vemurafenib was applied in. A few severe adverse events (mostly anemia and hyperbilirubinemia) were observed during treatment. CONCLUSIONS:The lack of evidence in responses observed regardless of what line of treatment vemurafenib was applied in suggests there is no clinical reason for restricting BRAF inhibitors to only the first line of therapy. Our study confirms that novel agents brought about a major advancement in the management of melanoma. In line with literature, BRAF inhibitors and ipilimumab significantly improved the antitumor response rate with manageable adverse events.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Polkowska M,Ekk-Cierniakowski P,Czepielewska E,Kozłowska-Wojciechowska Mdoi
10.1007/s00228-018-2590-6subject
Has Abstractpub_date
2019-03-01 00:00:00pages
329-334issue
3eissn
0031-6970issn
1432-1041pii
10.1007/s00228-018-2590-6journal_volume
75pub_type
杂志文章abstract:PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02842-y
更新日期:2020-05-01 00:00:00
abstract:OBJECTIVE:Little is known about patient compliance with oral adjuvant chemotherapy. It is estimated to be poor especially in Japan, where it is still unusual for patients to be directly informed of their diagnosis of malignancy. 5-Fluorouracil (5-FU) was measured in hair samples to assess patient exposure to 5-FU, and ...
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/s002280050077
更新日期:1996-01-01 00:00:00
abstract:OBJECTIVE:To investigate the influence of theophylline on erythropoiesis in chronic obstructive pulmonary disease (COPD) and explore the potential underlying mechanisms. METHODS:We evaluated the haematological parameters and erythropoietin (EPO) values in 38 COPD patients, 18 of which had been treated with theophyllin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0640-0
更新日期:2003-09-01 00:00:00
abstract::The effect of procainamide (P) on left ventricular function as measured by the systolic time intervals (STI) was studied in 14 patients with primary myocardial disease. P, 7.5 mg/kg body weight, was given intravenously at a rate of 100 mg per minute. Administration of P produced a decrease in left ventricular performa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561387
更新日期:1980-10-01 00:00:00
abstract:OBJECTIVE:Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illn...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050402
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist. METHODS:Clazosentan was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-006-0117-z
更新日期:2007-02-01 00:00:00
abstract::In the 3rd paragraph and 2nd line of the Conclusion section the correct sentence should be: It is now important to encourage policy and decision makers to facilitate and accommodate future linkage of data. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00228-017-2358-4
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:This study aimed to estimate the total healthcare costs associated with elderly chronic pain (CP) patients, define cost-related factors in this population, and examine cost evolution over two years. METHOD:This is an ancillary study from the CP S.AGE subcohort, including non-institutionalized patients aged o...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1871-6
更新日期:2015-08-01 00:00:00
abstract::The effect of ethanol intake on disopyramide elimination was examined in an open crossover study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the uri...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544024
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVES:To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS:The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0666-3
更新日期:2003-11-01 00:00:00
abstract:PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine wh...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-015-1934-8
更新日期:2015-12-01 00:00:00
abstract::Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental...
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/BF00194948
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:To comparatively assess the prevalence rates of potentially inappropriate medications (PIMs) obtained by the former and latest versions of American Geriatrics Society Beers Criteria (AGS BC) and screening tool of older person's potentially inappropriate prescriptions (STOPP), and analyze the factors of influenc...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02722-0
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 20...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03046-0
更新日期:2020-11-17 00:00:00
abstract::Human calcitonin (hCT) injected into the lumen of the descending colon of normal human subjects was absorbed within minutes and could be recognized intact in plasma as shown by RIA in combination with reverse-phase HPLC. The absorption was low and variable, with bioavailabilities ranging from 0.01% to 2.7% relative to...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02285096
更新日期:1992-01-01 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::The effects of acute and chronic administration of a slow-release preparation of pinacidil have been studied in eight normotensive volunteers aged 40-57 years. Continuous administration of 20 mg b.i.d. pinacidil had no effect on serum pinacidil concentrations measured as AUC (0-9 h), but accumulation of the principal ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00555515
更新日期:1988-01-01 00:00:00
abstract::The effect of spironolactone on cardiac contractility indices was studied by externally recording systolic time intervals in four digitalized and four non-digitalized patients with ischaemic heart disease. A negative inotropic effect was found after spironolactone 100mg b.i.d. in all eight patients, as measured by an ...
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/BF00637612
更新日期:1982-01-01 00:00:00
abstract::Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01037943
更新日期:1983-01-01 00:00:00
abstract::The duration of action of tiapamil was assessed in ten patients with stable exertional angina. Maximal symptom-limited treadmill exercise electrocardiography was performed before and at 1, 3, 6 and 9 h after therapy. Significant differences were only found at 1 h after tiapamil with increases in mean exercise duration...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543965
更新日期:1987-01-01 00:00:00
abstract::The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thu...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00870989
更新日期:1986-01-01 00:00:00
abstract::Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00279976
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS:CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS:The frequency f...
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/s002280100264
更新日期:2001-04-01 00:00:00
abstract:PURPOSE:Concomitant treatment with the glucose-lowering drug metformin and the platelet aggregation inhibitor dipyridamole often occurs in patients with type 2 diabetes mellitus who have suffered a cerebrovascular event. The gastrointestinal uptake of metformin is mediated by the human equilibrative nucleoside transpor...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2039-8
更新日期:2016-06-01 00:00:00
abstract:OBJECTIVE:To examine the association between the sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of lung cancer. METHOD:Meta-analysis of case-control studies using a random effects model. The "Main outcome measure" was the odds ratio for the risk of lung cancer, using extensive metabolisers as the ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s002280050219
更新日期:1997-01-01 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::The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558077
更新日期:1989-01-01 00:00:00
abstract::The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00266354
更新日期:1992-01-01 00:00:00
abstract::The efficacy of bopindolol and atenolol in the treatment of patients with chronic stable angina pectoris have been compared in a double blind, randomized study. Both bopindolol 1 mg and atenolol 100 mg for 6 weeks increased mean exercise time (25% and 22%, respectively, compared to placebo), time to angina (27% and 25...
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/BF00314809
更新日期:1990-01-01 00:00:00
abstract::The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
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/BF00542319
更新日期:1982-01-01 00:00:00