The European medicines agency review of Bosutinib for the treatment of adult patients with chronic myelogenous leukemia: Summary of the scientific assessment of the committee for medicinal products for human use
Hanaizi Z.,European Medicines Agency |
Unkrig C.,Bundesinstitut For Arzneimittel Und Medizinprodukte |
Enzmann H.,Bundesinstitut For Arzneimittel Und Medizinprodukte |
Camarero J.,Hospital Puerta Of Hierro |
And 5 more authors.
Oncologist | Year: 2014
On March 27, 2013, a conditionalmarketing authorization valid throughout the European Union was issued for bosutinib (Bosulif) for the treatment of adult patientswith chronic-phase, accelerated-phase, and blast-phase Philadelphia chromosome positive (Ph+) chronicmyelogenous leukemia (CML) previously treated with one tyrosine kinase inhibitor or more and for whom imatinib, nilotinib, and dasatinib are not considered appropriate treatment options. Bosutinib is a kinase inhibitor that targets the BCR-ABL kinase.The recommended dose is 500 mg of bosutinib once daily. The main evidence of efficacy for bosutinib was based on a CML subgroup analysis of study 3160A4-200, a phase I/II study of bosutinib in Ph+ leukemia in imatinib-resistant or intolerant CML.The subgroup was defined based on the presence of a BCR-ABL kinase domain mutation that would be expected to confer resistance to dasatinib (F317, E255) or nilotinib (E255, Y253, F359) and expected to have sensitivity to bosutinib or based on the presence of medical conditions or prior toxicities thatmay predispose the patient to unacceptable risk in the setting of nilotinib or dasatinib therapy. A conditional marketing authorization was granted because of the limited evidence of efficacy and safety currently supporting this last-line indication. © AlphaMed Press 2014.
Wessely R.,Zentrum fur Herz Gefaess und Lungenmedizin Mediapark |
Marzocchi A.,Policlinico S. Orsola Malpighi |
Schwacke H.,Krankenhaus der Ev. Diakonieanstalt |
Bertel O.,Klinik im Park |
And 6 more authors.
Journal of Interventional Cardiology | Year: 2013
Background To date, no published data are available regarding long-term follow-up of new generation DES implanted in coronary artery bypass graft (CABG) lesions. Objectives To assess the long-term clinical outcome of patients receiving the new generation Biolimus A9-coated drug-eluting stent (DES) with biodegradable polymer in saphenous vein grafts (SVG). Methods Three thousand sixty-seven patients were included in the NOBORI 2 registry: 71 patients with a total of 117 lesions received at least 1 biolimus A9 DES in SVG lesions and 2,959 patients received percutaneous coronary intervention in other lesions. Clinical follow-up was performed at 1, 6, and 12 months, and annually up to 3 years. Results Compared to the non-CABG group, patients with CABG lesions were older (P < 0.001), had a higher Charlson Comorbidity Index (P = 0.004), and presented more often with acute coronary syndrome (P = 0.02). At 3-year follow-up, cardiac death occurred in 9.7% versus 2.1% (P < 0.001), myocardial infarction (MI) in 8.3% versus 3.0% (P = 0.02), target lesion failure in 13.9% versus 6.4% (P = 0.03), and major adverse cardiac event in 18.1% versus 8.6% (P = 0.01). No differences were observed in TV-MI and TLR, nor stent thrombosis (ST) which was generally low in both groups (1.4% vs 0.8%, P = NS). Conclusion Albeit 3-year outcomes were less favorable in the CABG group, the higher cardiac mortality was apparently not driven by ST, target vessel MI, or TLR, but is likely due to advanced disease and age as well as comorbidity. The low TLR rate as well as the absence of late and very late ST suggest that BES are safe and effective for the treatment of CABG lesions. © 2013, Wiley Periodicals, Inc.
Danzi G.B.,Fondazione IRCCS Ca Granda |
Chevalier B.,Institute Cardiovasculaire Paris Sud |
Urban P.,Hopital de la Tour |
Fath-Ordoubadi F.,Royal Infirmary |
And 13 more authors.
EuroIntervention | Year: 2012
Aims: Previous studies for approved indications (on-label) have shown the good safety and efficacy profiles of the Nobori DES. We conducted a prospective, multicentre study to validate the clinical performance of this stent in a real-world setting.Methods and results: A total of 3,067 consecutive patients undergoing a percutaneous coronary intervention with the Nobori DES were enrolled in the NOBORI 2 registry. At one and two years, 97% and 95% of patients, respectively, were available for follow-up. The rates of target lesion failure (TLF), cardiac death, myocardial infarction and target lesion revascularisations were: 3.9%, 1.2%, 1.9% and 2.2% at one year and 5.1%, 1.6%, 2.4% and 3.0% at two years. Overall, 2,242 patients (73%) were treated for at least one off-label indication. When comparing off-label and on-label groups, the results were: TLF 4.5% vs. 2.2%, p=0.003 at one year and 5.9% vs. 2.8%, p=0.001 at two years. The rate of stent thrombosis was 0.68%, and 0.80% at one and two years, respectively with no difference between the off-label and on-label groups (0.76% vs. 0.48%, p=0.6 and 0.89% vs. 0.61%, p=0.5).Conclusions: The promising results previously observed in lower risk patients can be replicated in daily practice. As expected, in off-label indications, rates of adverse events were higher. Nevertheless, our results suggest the good and sustained performance of this stent system in high-risk patients with significant comorbidities and/or complex lesions. (Clinical trial registration: ISRCTN81649913; http://www.controlled-trials.com/isrctn/search.html?srch= 81649913&sort=3&dir=desc&max=10). © Europa Edition 2012. All rights reserved.
The european medicines agency review of pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressivenon-hodgkin's B-celllymphomas:Summaryofthescientific assessmentof the committee for medicinal products for human use
Pean E.,European Medicines Agency |
Flores B.,Medicines and Healthcare Products Regulatory Agency |
Hudson I.,Medicines and Healthcare Products Regulatory Agency |
SjoBerg J.,Medical Products Agency |
And 5 more authors.
Oncologist | Year: 2013
On May 10, 2012, the European Commission issued a conditional marketing authorization valid throughout the European Union for pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphoma (NHL). Pixantrone is a cytotoxic aza-anthracenedione that directly alkylates DNAforming stable DNA adducts and cross-strand breaks. The recommended dose of pixantrone is 50 mg/m2 administered on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles. In the main study submitted for this application, a significant difference in response rate (proportion of complete responses and unconfirmed complete responses) was observed in favor of pixantrone (20.0% vs. 5.7% for pixantrone and physician's best choice, respectively), supported by the results of secondary endpoints of median progression- free and overall survival times (increase of 2.7 and 2.6 months, respectively). The most common side effects with pixantrone were bone marrow suppression (particularly of the neutrophil lineage) nausea, vomiting, and asthenia. This article summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu).© AlphaMed Press 2013.
The european medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: Summary of the scientific assessment of the committee for medicinal products for human use
Hanaizi Z.,European Medicines Agency |
Flores B.,Medicines and Healthcare Products Regulatory Agency |
Hemmings R.,Medicines and Healthcare Products Regulatory Agency |
Camarero J.,Agencia Espanola de Medicamentos y Productos Sanitarios |
And 5 more authors.
Oncologist | Year: 2015
On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM 1 LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM 1 LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rankp value,.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA © AlphaMed Press 2015.
Rutonjski L.,Oncology Institute of Vojvodina |
Petrovic B.,Oncology Institute of Vojvodina |
Baucal M.,Oncology Institute of Vojvodina |
Teodorovic M.,Oncology Institute of Vojvodina |
And 3 more authors.
Radiation Oncology | Year: 2012
Background: Independent external audits play an important role in quality assurance programme in radiation oncology. The audit supported by the IAEA in Serbia was designed to review the whole chain of activities in 3D conformal radiotherapy (3D-CRT) workflow, from patient data acquisition to treatment planning and dose delivery. The audit was based on the IAEA recommendations and focused on dosimetry part of the treatment planning and delivery processes.Methods: The audit was conducted in three radiotherapy departments of Serbia. An anthropomorphic phantom was scanned with a computed tomography unit (CT) and treatment plans for eight different test cases involving various beam configurations suggested by the IAEA were prepared on local treatment planning systems (TPSs). The phantom was irradiated following the treatment plans for these test cases and doses in specific points were measured with an ionization chamber. The differences between the measured and calculated doses were reported.Results: The measurements were conducted for different photon beam energies and TPS calculation algorithms. The deviation between the measured and calculated values for all test cases made with advanced algorithms were within the agreement criteria, while the larger deviations were observed for simpler algorithms. The number of measurements with results outside the agreement criteria increased with the increase of the beam energy and decreased with TPS calculation algorithm sophistication. Also, a few errors in the basic dosimetry data in TPS were detected and corrected. Conclusions: The audit helped the users to better understand the operational features and limitations of their TPSs and resulted in increased confidence in dose calculation accuracy using TPSs. The audit results indicated the shortcomings of simpler algorithms for the test cases performed and, therefore the transition to more advanced algorithms is highly desirable. © 2012 Rutonjski et al.; licensee BioMed Central Ltd.
Verhagen P.C.M.S.,Erasmus Medical Center |
Wildhagen M.F.,Erasmus Medical Center |
Verkerk A.M.,Erasmus Medical Center |
Vjaters E.,Riga Stradins University |
And 8 more authors.
World Journal of Urology | Year: 2013
Background: To compare intermittent treatment (IT) versus continuous treatment (CT) using cyproterone acetate (CPA) in bone metastatic prostate cancer patients, we conducted an open-label, multicenter randomized trial. Continuous androgen deprivation therapy is the standard treatment in metastatic prostate cancer. Intermittent treatment might maintain efficacy while toxicity and costs are reduced. Methods: Patients received CPA 100 mg tid in the prephase. Patients with a PSA decline of ≥90 % or PSA <4 ng/ml were randomized. If patients were progressive, LHRH analogues were added. Primary end point was time to PSA progression. Results: A total of 366 patients were recruited; 258 reached a good response after 3 or 6 months and were randomized. A total of 131 patients randomized to IT and 127 to CT. Patients on IT had an average of 1.7 episodes on CPA, before LHRH analogues were started. The mean time without treatment in IT was 463 days versus 422 days on treatment. There were statistical significant differences between IT and CT in 3 of the 5 functional scales of EORTC QLQ C 30; however, the clinical relevance of this finding appears modest. Symptom and potency scales showed significant advantages for IT. There were no differences in time to PSA progression on CPA, time to PSA and/or clinical progression on LHRH analogues and time to cancer-specific and overall survival. Conclusions: IT by CPA is associated with less symptoms and modest advantages in QOL domains. There were no differences in time to PSA progression, clinical progression or survival. © 2013 Springer-Verlag Berlin Heidelberg.
Bachmann M.,Tallinn University of Technology |
Suhhova A.,Tallinn University of Technology |
Lass J.,Tallinn University of Technology |
Aadamsoo K.,North Estonia Regional Hospital |
And 2 more authors.
IFMBE Proceedings | Year: 2014
Diagnosis of depression is still based mainly on evaluation of the intensity of subjective and clinical symptoms by psychiatrists. This study is aimed to give additional objective information about depression analyzing the electroencephalographic (EEG) signal using the method of detrended fluctuation analysis (DFA). DFA is applied to evaluate the presence and persistence of long range correlations in time in EEG signals. EEG recordings were carried out on the groups of depressive and healthy subjects of 18 female volunteers each. The DFA was calculated on EEG signals from P3-Pz channel at a length of 5 minutes. The DFA method revealed statistically significant difference between healthy and depressive subjects. Resting EEG of healthy subjects exhibited persistent long-range correlation in time. In depression the long-range correlation was less persistent and for about half of the depressed subjects (44%) the EEG revealed long-range anti-correlation in time. © Springer International Publishing Switzerland 2014.
Kaldmae M.,Tallinn University |
Zilmer M.,University of Tartu |
Viigimaa M.,North Estonia Regional Hospital |
Zemtsovskaja G.,North Estonia Regional Hospital |
And 3 more authors.
Upsala Journal of Medical Sciences | Year: 2011
Background. Cardiovascular diseases (CVD) are associated with significant morbidity and mortality, which is highest in Eastern Europe including Estonia. Accumulating evidence suggests that life-style is associated with the development of CVD. The aim of this study was to evaluate the informative power of common CVD-related markers under unhealthy conditions. Subjects. Subjects (n = 51; mean age 45 years; 90% men) were recruited from a shelter for homeless people in Tallinn, Estonia, and consisted of persons who constantly used alcohol or surrogates, smoked, and were in a bad physical condition (amputated toes, necrotic ulcers, etc.). Methods. Blood pressure, pulse rate, and waist circumference were measured, and body mass index (BMI) was calculated. The following markers were measured in blood serum: total cholesterol (TChol), high-density lipoprotein cholesterol (HDL-Chol), low-density lipoprotein cholesterol (LDL-Chol), plasma triglycerides (TG), apolipoproteins A-l (ApoA1) and B (ApoB), lipoprotein(a) (Lp(a)), glycated hemoglobin (HbA1c), glucose (Gluc), high-sensitivity C-reactive protein (hsCRP), serum carbohydrate- deficient transferrin (CDT), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Except smoking, the anamnestic information considering eating habits, declared alcohol consumption and medication intake were not included in the analysis due to the low credibility of self-reported data. Results. More than half of the investigated patients had values of measured markers (hsCRP, TChol, LDL-Chol, TG, HbA1c, ApoA1, ApoB, Lp(a), Gluc) within normal range. Surprisingly, 100% of subjects had HDL-Chol within endemic norm. Conclusion. This study demonstrates that traditional markers, commonly used for prediction and diagnosis and treatment of CVD, are not always applicable to homeless people, apparently due to their aberrant life-style. © 2011 Informa Healthcare.
PubMed | North Estonia Regional Hospital, Hospital Puerta Of Hierro, University Hospital Brno, Institute for Cardiovascular Disease Dedinje and 11 more.
Type: Journal Article | Journal: Heart (British Cardiac Society) | Year: 2016
To evaluate the long-term follow-up of the unrestricted use of a biodegradable polymer-coated drug-eluting stent in patients undergoing percutaneous coronary intervention (PCI).The Nobori 2 study was a prospective, multicentre, observational registry evaluating the safety and the efficacy of the biodegradable polymer biolimus-eluting stent (BP-BES) among 3067 patients recruited at 125 international sites. The primary combined endpoint was a composite of cardiac death, myocardial infarction and target-lesion revascularisation (TLR).Five-year follow-up was available in 2738 (89.3%) patients. The combined endpoint occurred in 268 patients (10%, 95% CIs 8.9% to 11.3%) at 5 years, with 3.9% of events during the first year and 6.2% during years 1-5 of follow-up. Cumulative rates of TLR and definite/probable stent thrombosis were 5.3% (95% CI 4.5% to 6.3%) and 1.1% (95% CI 0.8% to 1.6%), respectively. Between 1 and 5years, TLR and very late stent thrombosis rates were 3.5% (95% CI 2.8% to 4.4%) and 0.6% (95% CI 0.3% to 1.1%), respectively. Previous PCI (HR, 2.05, 95% CI 1.68 to 2.50), moderate-to-severe renal disease (HR, 1.89, 95% CI 1.30 to 2.74) and peripheral vascular disease (HR, 1.86, 95% CI 1.38 to 2.52) were the three most powerful independent predictors of the combined endpoint at 5 years.The final 5-year follow-up of the Nobori 2 registry demonstrates the safety and effectiveness of the BP-BES in an unselected, broadly inclusive cohort of PCI patients, highlighting the excellent performance of this coronary stent technology after polymer biodegradation.ISRCTN81649913; Results.