Masarykuv onkologicky ustav

Brno, Czech Republic

Masarykuv onkologicky ustav

Brno, Czech Republic
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Baselga J.,Harvard University | Baselga J.,SOLTI Breast Cancer Research Group | Bradbury I.,Frontier Science Scotland | Bradbury I.,Queen's University of Belfast | And 28 more authors.
The Lancet | Year: 2012

Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer. We argue that the two anti-HER2 agents given together would be better than single-agent therapy. Methods: In this parallel groups, randomised, open-label, phase 3 study undertaken between Jan 5, 2008, and May 27, 2010, women from 23 countries with HER2-positive primary breast cancer with tumours greater than 2 cm in diameter were randomly assigned to oral lapatinib (1500 mg), intravenous trastuzumab (loading dose 4 mg/m 2, subsequent doses 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab. Treatment allocation was by stratified, permuted blocks randomisation, with four stratification factors. Anti-HER2 therapy alone was given for the first 6 weeks; weekly paclitaxel (80 mg/m 2) was then added to the regimen for a further 12 weeks, before definitive surgery was undertaken. After surgery, patients received adjuvant chemotherapy followed by the same targeted therapy as in the neoadjuvant phase to 52 weeks. The primary endpoint was the rate of pathological complete response (pCR), analysed by intention to treat. This trial is registered with, NCT00553358. Findings: 154 patients received lapatinib, 149 trastuzumab, and 152 the combination. pCR rate was significantly higher in the group given lapatinib and trastuzumab (78 of 152 patients [51·3; 95 CI 43·1-59·5]) than in the group given trastuzumab alone (44 of 149 patients [29·5; 22·4-37·5]; difference 21·1, 9·1-34·2, p=0·0001). We recorded no significant difference in pCR between the lapatinib (38 of 154 patients [24·7, 18·1-32·3]) and the trastuzumab (difference -4·8, -17·6 to 8·2, p=0·34) groups. No major cardiac dysfunctions occurred. Frequency of grade 3 diarrhoea was higher with lapatinib (36 patients [23·4]) and lapatinib plus trastuzumab (32 [21·1]) than with trastuzumab (three [2·0]). Similarly, grade 3 liver-enzyme alterations were more frequent with lapatinib (27 [17·5]) and lapatinib plus trastuzumab (15 [9·9]) than with trastuzumab (11 [7·4]). Interpretation: Dual inhibition of HER2 might be a valid approach to treatment of HER2-positive breast cancer in the neoadjuvant setting. Funding: GlaxoSmithKline. © 2012 Elsevier Ltd.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2010.2.4.1-1 | Award Amount: 2.42M | Year: 2011

Cancer is a worldwide health burden and a major public health challenge in Europe, responsible for 25% of all deaths; a situation expected to worsen with population ageing. The strengthening of translational cancer research is an urgent need in European cancer research, i.e. the integration of basic, epidemiological, preclinical and clinical research with the implementation and evaluation of interventions in prevention, diagnosis, prognosis, treatment and care. The proposed ERA-NET TRANSCAN aims at linking translational cancer research funding programmes in 19 Member States and Associated Countries. By concentrating transnational resources TRANSCAN will provide a critical financial and scientific mass for tackling large scale problems, relevant for improving translational cancer research in each Member State or Associated Country as well as overall in Europe. The objectives of TRANSCAN will be achieved through interconnected activities, structured into six work packages (WP) and facilitated by the project coordination and management (WP1). A survey and analysis of national cancer research funding (WP2) will provide a comprehensive picture of the nature and extent of translational cancer research funding in the EU. Based on this knowledge, TRANSCAN will identify gaps in and opportunities for coordinated translational research, and will thus contribute to the development of a coordinated funding research policy shared by European countries. Based also on the outcome of these activities, three joint transnational calls for multinational translational cancer research programmes will be designed (WP3) and implemented (WP4). In this context, training programmes/activities of multi-disciplinary translational cancer research teams will be supported (WP5). The TRANSCAN performance will be monitored and confronted with the partners expectations, and a sustainability plan for the network beyond TRANSCAN will be elaborated (WP6), contributing to the building of a pan-European platform for translational cancer research.

Douillard J.-Y.,Center Rene Gauducheau | Siena S.,Ospedale Niguarda Ca Granda | Cassidy J.,The Beatson West of Scotland Cancer Center | Tabernero J.,University of Barcelona | And 17 more authors.
Annals of Oncology | Year: 2014

Background: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. Patients and methods: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. Results: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) forWT KRAS mCRC was 23.9 months (95%CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P=0.17 (68%OS events). An exploratory analysis of updated survival (>80%OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95%CI 0.70-0.98; P=0.03 forWT KRASmCRC. The adverse event profile was consistent with the primary analysis. Conclusions: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Petrakova K.,Masarykuv Onkologicky Ustav
Klinicka Farmakologie a Farmacie | Year: 2010

One of the principal therapeutic procedures in metastatic breast cancer is hormonal therapy. In patients with positive oestrogen receptors, it should be considered as first-line therapy, particularly due to its efficacy and good tolerability. Visceral metastases should not be a criterion in favour of chemotherapy over hormonal therapy. Since they are well tolerated, aromatase inhibitors are recommended as first-line hormonal therapy in postmenopausal patients. However, tamoxifen remains an acceptable option. The results of the recent CONFIRM and FIRST clinical trials support the use of 500 mg fulvestrant every four weeks in patients in whom prior hormonal therapy failed.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRADEV-3-2015 | Award Amount: 4.95M | Year: 2015

BBMRI-ERIC: the Biobanking and BioMolecular resources Research Infrastructure - European Research Infrastructure Consortium, aims to establish, operate and develop a Pan-European distributed research infrastructure in order to facilitate the access to biological resources as well as facilities and to support high quality biomolecular and biomedical research. The ADOPT BBMRI-ERIC proposal aims at boosting and accelerating implementation of BBMRI-ERIC and its services. Its main deliverables are designed to complete or launch the construction of key Common Services of the Research Infrastructure as required for ESFRI-projects under implementation, reflecting the targets of the European Research Area (ERA). One of the challenges in the post-genomic era is the research on common complex diseases, such as cancer, diabetes and Alzheimers disease. Revealing these diseases will depend critically on the study of human biological samples and data from large numbers of patients and healthy individuals. The EUs ageing population is will result in an increase in many of those diseases and consequently an increased healthcare expenditure for senior citizens. BBMRI-ERIC is a specific European asset having become a fundamental component in addressing the ongoing and future requirements particularly of Europes health service frameworks, including competitiveness and innovativeness of health-related industries. Its implementation is essential for the understanding of the diversity of human diseases, biological samples and corresponding data, which are required for the development of any new drug or diagnostic assay and are, therefore, critical for the advancement in health research, ultimately leading to personalised medicine. BBMRI-ERIC will provide a gateway access to the collections of the European research community, expertise and services building on the outcome of ADOPT BBMRI-ERIC.

De Bono J.S.,Institute of Cancer Research | Oudard S.,Hopital Europeen Georges Pompidou | Ozguroglu M.,Istanbul University | Hansen S.,University of Southern Denmark | And 9 more authors.
The Lancet | Year: 2010

Background Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment. Methods We undertook an open-label randomised phase 3 trial in men with metastatic castration-resistant prostate cancer who had received previous hormone therapy, but whose disease had progressed during or after treatment with a docetaxel-containing regimen. Participants were treated with 10 mg oral prednisone daily, and were randomly assigned to receive either 12 mg/m2 mitoxantrone intravenously over 15-30 min or 25 mg/m2 cabazitaxel intravenously over 1 h every 3 weeks. The random allocation schedule was computer-generated; patients and treating physicians were not masked to treatment allocation, but the study team was masked to the data analysis. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and safety. Analysis was by intention to treat. This study is registered at, NCT00417079. Findings 755 men were allocated to treatment groups (377 mitoxantrone, 378 cabazitaxel) and were included in the intention-to-treat analysis. At the cutoff for the final analysis (Sept 25, 2009), median survival was 15·1 months (95 CI 14·1-16·3) in the cabazitaxel group and 12·7 months (11·6-13·7) in the mitoxantrone group. The hazard ratio for death of men treated with cabazitaxel compared with those taking mitoxantrone was 0·70 (95 CI 0·59-0·83, p<0·0001). Median progression-free survival was 2·8 months (95 CI 2·4-3·0) in the cabazitaxel group and 1·4 months (1·4-1·7) in the mitoxantrone group (HR 0·74, 0·64-0·86, p<0·0001). The most common clinically significant grade 3 or higher adverse events were neutropenia (cabazitaxel, 303 [82] patients vs mitoxantrone, 215 [58]) and diarrhoea (23 [6] vs one [<1]). 28 (8) patients in the cabazitaxel group and five (1) in the mitoxantrone group had febrile neutropenia. Interpretation Treatment with cabazitaxel plus prednisone has important clinical antitumour activity, improving overall survival in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Funding Sanofi-Aventis. © 2010 Elsevier Ltd.

Metastatic breast cancer is an incurable disease. It is a chemosensitive disease in which chemotherapy significantly prolongs the survival of patients. Anthracyclines are among the most effective cytostatic drugs in the treatment for breast cancer. The major limitation of treatment is the cardiotoxicity of anthracyclines which increases after the cumulative dose is reached. The treatment of patients pretreated with adjuvant anthracyclines is thus problematic. Liposomal doxorubicin (Myocet) which has been shown to have equal efficacy to conventional anthracyclines, but lower cardiotoxicity in first-line treatment for metastatic disease in clinical trials seems to be a good alternative.

Head and neck tumours are the fourth most common cancer among men in Europe. The highest incidence is in the Mediterranean countries. The incidence rate of oropharyngeal cancer in the Czech Republic is 0.91/100 000 inhabitants with a mortality rate of 0.65/100 000 inhabitants; the most prevalent clinical stage of the tumour is clinical stage IV (58.9%). In palatine cancer, the incidence rate is 0.34/100 000 inhabitants with a mortality rate of 0.15/100 000 inhabitants. The most prevalent clinical stage is also clinical stage IV (26.7%). Women are significantly less affected than men, with the ratio of women to men being 4:1 in the Czech Republic. In terms of risk factors, smoking and alcohol consumption play a crucial role. The mean age of patients ranges from 50 to 60 years of age. The case reports present a patient with oropharyngeal cancer and another patient with cancer of the soft and hard palate and cancer of the palatine tonsil. In both cases, there were advanced local findings without distant metastases in "typical" male patients with a long-term alcohol and tobacco abuse.

The number of lymph nodes removed during the sentinel lymph node biopsy in patients with breast cancer usually ranges from 1 to 3. In some cases, multiple nodes are identified and removed, which could be associated with increased risk of postoperative morbidity. The objective of the study was to assess the number of sentinel lymph nodes removed in patients treated in our hospital, to analyze factors that may influence the amount of the removed nodes, and to find if there is an upper threshold number of lymph nodes that should be removed without sacrificing the diagnostic accuracy of the sentinel lymph node biopsy. Clinical data of four hundred and forty (440) breast cancer patients who underwent sentinel lymph node biopsy in Masaryk Memorial Cancer Institute during the year 2011 were retrospectively collected and analyzed. The number of sentinel lymph nodes ranged from 0 to 9 (average 1.7, median 1). The number of sentinel lymph nodes was significantly influenced by the age of the patient, the operating surgeon and the laterality of the surgery. In 275 cases the sentinel lymph nodes were negative, in the other cases macrometastases (n = 101), micrometastases (n = 46) or isolated tumor cells (n = 17) were found. In all the cases, but one, the staging of the axilla was determined by the status of the first three sentinel lymph nodes removed. Only in one case the first detected macrometastasis was present in the fifth node. In the vast majority of cases, the first three sentinel lymph nodes are sufficient to accurately assess the axillary status. However, with respect to the described case of first detected metastasis in the fifth node, to the present literary data and to the variability of clinical situations, we generally recommend to remove all lymph nodes meeting the criteria of the surgical definition of sentinel lymph node.

Univerzita Palackeho V Olomouci and Masarykuv Onkologicky Ustav | Date: 2010-10-20

The invention relates to a method for determining the sensitivity of patients suffering from a cancer disease towards targeted biological therapy based on the inhibition of signaling pathways of the members of HER family (e.g., HER-1, HER-2, HER-3 and HER-4) by determining the expression of the biomarker ribosomal protein S6 or its post-translationally modified form in the tumor.

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