The Dnepropetrovsk State Medical Academy was founded on September 15, 1916 from the Ekaterynoslavsky higher female courses Institute. The Institute acquired the status of State Academy in 1920 and it became the Dnepropetrovsk State Medical Academy in Ukraine in 1994.Official website : http://www.dpsmu.com Wikipedia.
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): A randomised phase 2 study
Finn R.S.,University of California at Los Angeles |
Crown J.P.,Irish Cooperative Oncology Research Group |
Lang I.,Orszagos Onkologiai Intezet |
Boer K.,Szent Margit Korhaz |
And 14 more authors.
The Lancet Oncology | Year: 2015
Background: Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. Methods: In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2·5 mg daily or continuous oral letrozole 2·5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Findings: Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29·6 months [95% CI 27·9-36·0] for the palbociclib plus letrozole group and 27·9 months [25·5-31·1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10·2 months (95% CI 5·7-12·6) for the letrozole group and 20·2 months (13·8-27·5) for the palbociclib plus letrozole group (HR 0·488, 95% CI 0·319-0·748; one-sided p=0·0004). In cohort 1 (n=66), median progression-free survival was 5·7 months (2·6-10·5) for the letrozole group and 26·1 months (11·2-not estimable) for the palbociclib plus letrozole group (HR 0·299, 0·156-0·572; one-sided p<0·0001); in cohort 2 (n=99), median progression-free survival was 11·1 months (7·1-16·4) for the letrozole group and 18·1 months (13·1-27·5) for the palbociclib plus letrozole group (HR 0·508, 0·303-0·853; one-sided p=0·0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events. Interpretation: The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway. © 2015 Elsevier Ltd.
Bondarenko A.,Dnipropetrovsk State Medical Academy |
Angrisani N.,University of Veterinary Medicine Hannover |
Meyer-Lindenberg A.,Ludwig Maximilians University of Munich |
Seitz J.M.,Leibniz University of Hanover |
And 2 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2014
The functions of some bone proteins, as osteopontin (OPN) and osteocalcin (OC), have been discovered by the latest studies. This fact suggests the possibility of their immunodetection to characterize peri-implant osteogenesis and implant impact on it. Cylindrical pins of Mg alloys (MgCa0.8, LAE442, ZEK100, LANd442) and titanium alloy (TiAl6V4) were implanted into the tibial medullae of 46 rabbits. Each group was divided regarding to implant duration (3 and 6 months). Bone samples adjacent to the implants were decalcified and treated with routine histological and immunohistochemical protocols using OC and OPN-antibodies. OC was detected in matrix of compact bone, but very rarely in osteoid and bone cells. OPN was detected intracellularly and in osteoid. After 3 months, the highest level of both markers was found in titanium group, followed by LAE442-group. In contrast to LAE442 and TiAl6V4, the other Mg alloys showed increasing levels of OC after 6 months. Lower levels of OP and OC compared to the control group are related to the continuous implant degradation and instability of bone-implant interface in early post-surgical period. Reduced marker's expression in LAE442 and TiAl6V4 groups after 6 months may indicate stabilization of bone-implant interface and completion of peri-implant neo-osteogenesis. Declining characters of OC and OPN expression over the implantation time, as well as their lowest levels in late post-surgical term, suggest a more appropriate biocompatibility of LAE442, which therefore seems to be the most preferable of the tested materials for the use in orthopaedic applications. © 2013 Wiley Periodicals, Inc.
Chow L.W.-C.,UNIMED Medical Institute |
Chow L.W.-C.,Organisation for Oncology and Translational Research OOTR |
Xu B.,Chinese Academy of Sciences |
Gupta S.,Tata Memorial Hospital |
And 5 more authors.
British Journal of Cancer | Year: 2013
Introduction:Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor that has demonstrated antitumour activity and an acceptable safety profile in patients with human epidermal growth factor receptor (HER)-2-positive breast cancer and other solid tumours.Methods:This was a phase I/II, open-label, two-part study. Part 1 was a dose-escalation study to determine the maximum tolerated dose (MTD) of neratinib plus paclitaxel in patients with solid tumours. Part 2 evaluated the safety, efficacy, and pharmacokinetics of the combination at the MTD in patients with HER2-positive breast cancer.Results:Eight patients were included in the dose-escalation study; no dose-limiting toxicities were observed, and an MTD of oral neratinib 240 mg once daily plus intravenous paclitaxel 80 mg m-2 on days 1, 8, and 15 of each 28-day cycle was determined. A total of 102 patients with HER2-positive breast cancer were enrolled in part 2. The overall median treatment duration was 47.9 weeks (range: 0.1-147.3 weeks). Common treatment-emergent adverse events (all grades/grade ≥3) included diarrhoea (92%/29%; none grade 4), peripheral sensory neuropathy (51%/3%), neutropenia (50%/20%), alopecia (46%/0%), leukopenia (41%/18%), anaemia (37%/8%), and nausea (34%/1%). Three (3%) patients discontinued treatment due to an adverse event (mouth ulceration, left ventricular ejection fraction reduction, and acute renal failure). Among the 99 evaluable patients in part 2 of the study, the overall response rate (ORR) was 73% (95% confidence interval (CI): 62.9-81.2%), including 7 (7%) patients who achieved a complete response; an additional 9 (9%) patients achieved stable disease for at least 24 weeks. ORR was 71% among patients with 0/1 prior chemotherapy regimen for metastatic disease and no prior lapatinib, and 77% among those with 2/3 prior chemotherapy regimens for metastatic disease with prior lapatinib permitted. Kaplan-Meier median progression-free survival was 57.0 weeks (95% CI: 47.7-81.6 weeks). Pharmacokinetic analyses indicated no interaction between neratinib and paclitaxel.Conclusion:The combination of neratinib and paclitaxel was associated with higher toxicity than that of neratinib as a single agent, but was manageable with antidiarrhoeal agents and dose reductions in general. The combination therapy also demonstrated a high rate of response in patients with HER2-positive breast cancer. A phase III trial is ongoing to assess the benefit and risk of this combination in the first-line setting. © 2013 Cancer Research UK. All rights reserved.
Schlachetzki J.C.M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Marxreiter F.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Regensburger M.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Kulinich A.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 3 more authors.
Restorative Neurology and Neuroscience | Year: 2014
Purpose: Parkinson's disease (PD) is characterized by striatal synaptic deafferentation followed by dopaminergic cell death in the substantia nigra pars compacta. Not only degenerative, but also regenerative, compensatory changes at distant sites of the primary lesion may occur in PD. The aim of the study was to analyze the temporal pattern of axonal and glial responses over a time course of six weeks post-lesioning. Methods: For this aim, 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle and both lesioned and non-lesioned striata were analyzed. Results: We detected increased tyrosine hydroxylase (TH) immunoreactivity within the non-lesioned striatum six weeks after injection indicative either of increased TH expression or compensatory neuritic changes. An increased number of microglial cells was present in both lesioned and unlesioned striata. There was no obvious change in microglial phenotype or in pro-inflammatory cytokine gene expression within the striatum without any apparent switch into a pro-inflammatory phenotype. No changes were observed in the number of mature oligodendrocytes. Conclusions: This temporal pattern shows, that the non-lesioned striatum undergoes profound changes, involving increased TH expression accompanied by a glial response. A better understanding of this complex interplay of neuronal as well as glial components not only within the lesioned, but also non-lesioned striatum may help to restore local neural circuits in PD. © 2014 - IOS Press and the authors. All rights reserved.
Lekhan V.,Dnipropetrovsk State Medical Academy
Health systems in transition | Year: 2010
The HiT profiles are country-based reports that provide a detailed description of a health system and of policy initiatives in progress or under development. HiTs examine different approaches to the organization, financing and delivery of health services and the role of the main actors in health systems; describe the institutional framework, process, content and implementation of health and health care policies; and highlight challenges and areas that require more in-depth analysis. The Ukrainian health system has preserved the fundamental features of the Soviet Semashko system against a background of other changes, which are developed on market economic principles. The transition from centralized financing to its extreme decentralization is the main difference in the health system in comparison with the classic Soviet model. Health facilities are now functionally subordinate to the Ministry of Health, but managerially and financially answerable to the regional and local self-government, which has constrained the implementation of health policy and fragmented health financing. Health care expenditure in Ukraine is low by regional standards and has not increased significantly as a proportion of gross domestic product (GDP) since the mid 1990s; expenditure cannot match the constitutional guarantees of access to unlimited care. Although prepaid schemes such as sickness funds are growing in importance, out-of-pocket payments account for 37.4% of total health expenditure. The core challenges for Ukrainian health care therefore remain the ineffective protection of the population from the risk of catastrophic health care costs and the structural inefficiency of the health system, which is caused by the inefficient system of health care financing. Health system weaknesses are highlighted by increasing rates of avoidable mortality. Recent political impasse has complicated health system reforms and policy-makers face significant challenges in overcoming popular distrust and fatigue in the face of necessary but as yet unimplemented reforms. World Health Organization 2010, on behalf of the European Observatory on health systems and Policies.
Belani C.P.,Penn State Hershey Cancer Institute |
Yamamoto N.,Wakayama Medical University |
Bondarenko I.M.,Dnipropetrovsk State Medical Academy |
Poltoratskiy A.,St. Petersburg State Medical University |
And 7 more authors.
BMC Cancer | Year: 2014
Background: The efficacy and safety of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). Methods: Overall, 170 patients were randomly assigned to receive axitinib at a starting dose of 5-mg twice daily continuously plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 of up to six 21-day cycles (arm I); axitinib on days 2 through 19 of each cycle plus pemetrexed/cisplatin (arm II); or pemetrexed/cisplatin alone (arm III). The primary endpoint was progression-free survival (PFS).Results: Median PFS was 8.0, 7.9, and 7.1 months in arms I, II, and III, respectively (hazard ratio: arms I vs. III, 0.89 [P = 0.36] and arms II vs. III, 1.02 [P = 0.54]). Median overall survival was 17.0 months (arm I), 14.7 months (arm II), and 15.9 months (arm III). Objective response rates (ORRs) for axitinib-containing arms were 45.5% (arm I) and 39.7% (arm II) compared with 26.3% for pemetrexed/cisplatin alone (arm III). Gastrointestinal disorders and fatigue were frequently reported across all treatment arms. The most common all-causality grade ≥3 adverse events were hypertension in axitinib-containing arms (20% and 17%, arms I and II, respectively) and fatigue with pemetrexed/cisplatin alone (16%). Conclusion: Axitinib in combination with pemetrexed/cisplatin was generally well tolerated. Axitinib combinations resulted in non-significant differences in PFS and numerically higher ORR compared with chemotherapy alone in advanced NSCLC.Trial registration: ClinicalTrials.gov: NCT00768755 (October 7, 2008). © 2014 Belani et al.; licensee BioMed Central Ltd.
Bondarenko I.,Dnipropetrovsk State Medical Academy |
Gladkov O.A.,Chelyabinsk Regional Clinical Oncology Center |
Elsaesser R.,Teva Ratiopharm |
Buchner A.,Teva Ratiopharm |
Bias P.,Teva Ratiopharm
BMC Cancer | Year: 2013
Background: Lipegfilgrastim is a novel glyco-pegylated granulocyte-colony stimulating factor in development for neutropenia prophylaxis in cancer patients receiving chemotherapy. This phase III, double-blind, randomized, active-controlled, noninferiority trial compared the efficacy and safety of lipegfilgrastim versus pegfilgrastim in chemotherapy-naïve breast cancer patients receiving doxorubicin/docetaxel chemotherapy.Methods: Patients with high-risk stage II, III, or IV breast cancer and an absolute neutrophil count ≥1.5 × 109 cells/L were randomized to a single 6-mg subcutaneous injection of lipegfilgrastim (n = 101) or pegfilgrastim (n = 101) on day 2 of each 21-day chemotherapy cycle (4 cycles maximum). The primary efficacy endpoint was the duration of severe neutropenia during cycle 1.Results: Cycle 1: The mean duration of severe neutropenia for the lipegfilgrastim and pegfilgrastim groups was 0.7 and 0.8 days, respectively (λ = -0.218 [95% confidence interval: -0.498%, 0.062%], p = 0.126), and no severe neutropenia was observed in 56% and 49% of patients in the lipegfilgrastim and pegfilgrastim groups, respectively. All cycles: In the efficacy population, febrile neutropenia occurred in three pegfilgrastim-treated patients (all in cycle 1) and zero lipegfilgrastim-treated patients. Drug-related adverse events in the safety population were reported in 28% and 26% of patients i006E the lipegfilgrastim and pegfilgrastim groups, respectively.Conclusion: This study demonstrates that lipegfilgrastim 6 mg is as effective as pegfilgrastim in reducing neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy.Trial Registration: Eudra EEACTA200901599910. The study protocol, two global amendments (Nos. 1 and 2), informed consent documents, and other appropriate study-related documents were reviewed and approved by the Ministry of Health of Ukraine Central Ethics Committee and local independent ethics committees (IECs). © 2013 Bondarenko et al.; licensee BioMed Central Ltd.
Bondarenko I.M.,Dnipropetrovsk State Medical Academy |
Bias P.,Teva Ratiopharm |
Buchner A.,Merckle GmbH
Supportive Care in Cancer | Year: 2016
Purpose: Lipegfilgrastim is a once-per-cycle, fixed-dose, glycoPEGylated recombinant granulocyte colony-stimulating factor (G-CSF) recently approved in Europe to reduce the duration of chemotherapy-induced neutropenia and incidence of febrile neutropenia in patients with cancer receiving chemotherapy. Bone pain-related (BPR) adverse events are commonly associated with G-CSF therapy. This post hoc analysis examined BPR treatment-emergent adverse events (TEAEs) in two comparative studies of lipegfilgrastim or pegfilgrastim in patients receiving chemotherapy. Methods: A post hoc analysis was conducted using integrated data from two double-blind randomized studies in patients with breast cancer receiving docetaxel and doxorubicin and treated prophylactically with subcutaneous lipegfilgrastim 6 mg or pegfilgrastim 6 mg once per cycle. BPR TEAEs were defined as arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, noncardiac chest pain, and pain in extremity. Relationship of BPR TEAEs to study treatment or chemotherapy was also reported by the investigators. Results: The analysis included 306 patients (lipegfilgrastim: n = 151; pegfilgrastim: n = 155). The proportion of patients experiencing BPR TEAEs was similar with lipegfilgrastim and pegfilgrastim (25.2 vs 21.9 %, respectively), as was the proportion of patients experiencing BPR treatment-emergent adverse drug reactions (TEADRs) (18.5 vs 16.8 %, respectively). No BPR TEADRs were serious, and none led to discontinuation. Conclusions: Nonsevere BPR TEAEs and TEADRs were observed in patients with breast cancer receiving chemotherapy and G-CSF; rates of BPR events were similar between lipegfilgrastim and pegfilgrastim. The similar BPR safety profile of lipegfilgrastim and pegfilgrastim provides support for use in patients with breast cancer receiving chemotherapy. © 2015, Springer-Verlag Berlin Heidelberg.
Lalk M.,University of Veterinary Medicine Hannover |
Reifenrath J.,University of Veterinary Medicine Hannover |
Angrisani N.,University of Veterinary Medicine Hannover |
Bondarenko A.,Dnipropetrovsk State Medical Academy |
And 3 more authors.
Journal of Materials Science: Materials in Medicine | Year: 2013
Biocompatibility and degradation of magnesium sponges (alloy AX30) with a fluoride (MgF2 sponge, n = 24, porosity 63 ± 6 %, pore size 394 ± 26 μm) and with a fluoride and additional calcium-phosphate coating (CaP sponge, n = 24, porosity 6 ± 4 %, pore size 109 ± 37 μm) were evaluated over 6, 12 and 24 weeks in rabbit femurs. Empty drill holes (n = 12) served as controls. Clinical and radiological examinations, in vivo and ex vivo μ-computed tomographies and histological examinations were performed. Clinically both sponge types were tolerated well. Radiographs and XtremeCT evaluations showed bone changes comparable to controls and mild gas formation. The μCT80 depicted a higher and more inhomogeneous degradation of the CaP sponges. Histomorphometrically, the MgF2 sponges resulted in the highest bone and osteoid fractions and were integrated superiorly into the bone. Histologically, the CaP sponges showed more inflammation and lower vascularization. MgF2 sponges turned out to be better biocompatible and promising, biodegradable bone replacements. © 2012 Springer Science+Business Media New York.
Mayer L.,Mount Sinai School of Medicine |
Sandborn W.J.,University of California at San Diego |
Stepanov Y.,Dnipropetrovsk State Medical Academy |
Geboes K.,Catholic University of Leuven |
And 8 more authors.
Gut | Year: 2014
Objective Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. Design In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure-response relationship and histological improvement. Results 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108-235 μg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. Conclusions Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose-response studies are warranted.