[Show abstract][Hide abstract] ABSTRACT: Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease. We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response. Methods. A total of 79 patients with metastatic renal cell carcinoma were included in our study. miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR. Normalized data were subjected to ROC and Kaplan-Meier analysis. Results. We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5.8 versus 12.8 months, miR-484: median TTP 5.8 versus 8.9 months). Conclusion. miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy. miR-155 is a known oncogene with direct influence on neovascularization. Biological role of miR-484 has to be clarified. Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Children with high-grade glioma still have a poor prognosis despite the use of multimodal therapy including surgery, radiotherapy, and chemotherapy. New therapeutic strategies and methods evaluating such therapies are needed.
Here we describe a child with anaplastic oligodendroglioma of the spinal cord who was unable to tolerate standard chemoradiotherapy and who had still-vital residual tumour during therapy. A good response was obtained with low-dose metronomic treatment containing vinblastine. The treatment was guided according to gradual response assessed using various positron-emission tomography tracers.
Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.
[Show abstract][Hide abstract] ABSTRACT: Bevacizumab, a humanized monoclonal IgG antibody against the vascular endothelial growth factor (VEGF), is reimbursed in combination with chemotherapy for the first and subsequentline treatment of patients with metastatic colorectal cancer (mCRC) in the Czech Republic. However, its high cost is a potentially limiting factor. We assessed the cost of bevacizumab in the treatment of mCRC in a comprehensive cancer center.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 08/2014; 27(4):255-60. DOI:10.14735/amko2014255
[Show abstract][Hide abstract] ABSTRACT: Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer. Key words: vitamin D - 25- hydroxyvitamin D - vitamin D receptor - breast cancer This work was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) and by MH CZ - DRO (MMCI, 00209805) and BBMRI_CZ (LM2010004). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biomedical papers.Submitted: 29. 1. 2014Accepted: 5. 5. 2014.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 06/2014; 27(Supplementum):143-149. DOI:10.14735/amko20141S143
[Show abstract][Hide abstract] ABSTRACT: Cancer represents one of the main causes of death among diseases across the age spectrum. Tumors in children, however, represent less than 1% of the total number of cancers in the population and in terms of the definition of orphan diseases in Europe are all children's cancers considered as orphan diseases. This is the reason why the research and development of new agents against cancer in childhood stands outside of the main interest. Every year around 30,000 new cases of cancer in children and adolescents are diagnosed in the European Unioun (EU) and approximately 80% of them achieve long-term remission using mainly conventional methods of treatment. However, almost 6,000 children and adolescents die every year of malignant tumors therefore cancer remains a major cause of morbidity and mortality. Consequently, there is a demand for new and safe drugs for children suffering from cancer which would lead to improved survival and to risk reduction of late adverse effects of cancer treatment. In the past 10 years in the EU, more in the EU-15 than in our country, 20 performed oncology trials in phase I involving adults account for only one trial in pediatric patients. The issue of new drugs clinical testing in rare cancers is very complex, complicated and for current unsatisfactory situation might be responsible various aspects. These aspects contain the legislative field, the problem of determining the correct dose of testing drug as a single agent or in combination therapy, the use of testing drug in advanced disease or already in de novo diagnosed patients, as well as equity (equal) access to new drugs being tested, the goal set for each molecule/drug in clinical trials, the conflict of interest balanced with sufficient professionalism and last but not least, the need for new methodologies and statistical approaches. The aim of this article is to describe the issue complexity of incorporation of new, modern drug for cancer patients with orphan diseases, including children.Key words: clinical evaluation - new drugs - orphan diseases in oncology.
[Show abstract][Hide abstract] ABSTRACT: With the recent addition of anti-angiogenic agents to cancer treatment, the angiogenesis regulators in platelets are gaining importance. Platelet factor 4 (PF-4/CXCL4) and Connective tissue activating peptide III (CTAP-III) are two platelet-associated chemokines that modulate tumor angiogenesis, inflammation within the tumor microenvironment, and in turn tumor growth. Here, we review the role of PF-4 and CTAP-III in the regulation of tumor angiogenesis; the results of clinical trial using recombinant PF-4 (rPF-4); and the use of PF-4 and CTAP-III as cancer biomarkers.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Evaluation of the cost and effectiveness of therapy for patients with the wet form of age-related macular degeneration (AMD) in routine clinical practice. Methods: A retrospective multicentre evaluation of changes in the best-corrected visual acuity in applied kinds of therapy and a comparison with the cost of individual therapeutic procedures. Results: An overall total of 788 eyes of 763 patients with an average age of 73.2 ± 8.6 years was evaluated for a 1-year minimum period. In the ranibizumab and pegaptanib therapy groups, a reduction of 1.3 letters (p = 0.303) and 1.4 letters (p = 0.197) was found, respectively. In the group of photodynamic therapy (PDT) with verteporfin, a reduction of 5.2 letters was achieved (p < 0.001). Under the conditions of routine practice in the Czech Republic, the annual cost is highest (EUR 5,467.63/patient) in patients with pegaptanib therapy. The annual cost in patients with ranibizumab therapy is lower by EUR 1,220.16. The cost is nearly half (EUR 2,783.65) in the group treated with PDT with verteporfin. Conclusion: An initiation of AMD therapy by ranibizumab is cost-effective as compared to pegaptanib. Both ranibizumab and pegaptanib are significantly more efficient as compared to PDT with verteporfin. Therapy with ranibizumab and pegaptanib, as compared to PDT with verteporfin, prevents the loss of 1 line of vision on the ETDRS chart for EUR 1,225.98 and 2,286.18, respectively.
[Show abstract][Hide abstract] ABSTRACT: Vitamin D is an endogenous product of mammalian organisms from which an active agent of a steroid hormone nature is synthesized. These hormones participate in a variety of key metabolic processes in every nuclear cell, whether on endocrine, paracrine and autocrine or subcellular level. Vitamin D represents a very interesting molecule which participates in a great deal of body processes. This review summarizes the findings about the metabolism of vitamin D focusing on pathophysiology of malignant diseases. Keywords: vitamin D - malignant diseases - metabolism of vitamin D - anticancer effects of vitamin D.
[Show abstract][Hide abstract] ABSTRACT: The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers.
COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled.
The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3-69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children.
COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.
[Show abstract][Hide abstract] ABSTRACT: Phase I trials in oncology usually enrolling patients with advanced disease who have failed standard treatment options. The primary endpoint of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid unnecessary exposure of patients to sub-therapeutic doses of an agent. The mission of phase I clinical trials is to accelerate the development of new anticancer drugs with the purpose of improving quality of life and survival for patients with cancer.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2012; 25 Suppl 2:2S98-101.
[Show abstract][Hide abstract] ABSTRACT: CD3+ CD56+ NKT-like cells have been shown to produce substantial amounts of pro-inflammatory cytokines and to mediate lysis of malignant cells. Using flow cytometry, we evaluated the absolute NKT-like cell count in peripheral blood from individuals in a reference population and the median number was 0.085 x 10(9)/l. The average number of NKT-like cells in patients with disseminated cancer was 2.65 fold higher than in the reference population. The number of CD3+ CD56+ cells in solid tumour patients who achieved complete remission was comparable to the reference population. In breast cancer patients with initially (prior to therapy) increased number of NKT-like cells, we observed a trend toward longer disease-free survival. Thus we conclude that CD3+ CD56+ NKT-like cells have potential to suppress tumour evasion and are expanded in peripheral blood of some epithelial tumour patients.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2012; 25 Suppl 2:2S21-5.
[Show abstract][Hide abstract] ABSTRACT: VOD Zhoubné onemocnění tlustého střeva (dg. C18), rektosig-moideálního spojení (C19) a konečníku (C20) je jednou z nej-častějších malignit v České republice. Nejčastější léčebnou modalitou u kolorektálního karcinomu je kurativní resekce ná-doru. Pacientům s karcinomem tlustého střeva klinického sta- Karlova v Praze, Lékafiská fakulta Hradec Králové, Ústav klinické biochemie a diagnostiky FN 3 P & R LAB a.s., Nov˘ Jiãín 4 CGB laboratofi a.s., Ostrava 5 Univerzila Palackého v Olomouci, Ústav molekulární a translaãní medicíny LF 6 Fakultní Thomayerova nemocnice s poliklinikou v Praze, Oddûlení patologie a molekulární medicíny 7 Bioptická laboratofi s.r.o., PlzeÀ 8 Univerzita Karlova v Praze, 1. lékafiská fakulta, Ústav patologie VFN 9 Univerzita Karlova v Praze, Lékafiská fakulta Hradec Králové, FingerlandÛv ústav patologie FN SOUHRN
[Show abstract][Hide abstract] ABSTRACT: Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status--out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.
[Show abstract][Hide abstract] ABSTRACT: Targeted biologic therapy has been proven to be effective compared to the current therapy of metastatic renal cell carcinoma (mRCC) in clinical studies as well as in actual clinical practice, but its high cost is a potentially limiting factor. Since the local cost-effectiveness analysis is missing, we assessed the cost of sunitinib and sorafenib in the treatment of mRCC in a comprehensive cancer centre.
A total of 31 patients were treated with sunitinib and/or sorafenib between 06/2006 and 09/2009 and then followed for at least 12 months. Clinical (disease progression, adverse events, dose reduction) and cost data (medication, examination, hospitalization) were assessed in the comprehensive cancer centre (1 Euro = 25.78 CZK).
The multikinase inhibitors were the second line treatment for most patients after INF-alpha therapy failure (86.7%). The mean cost per month to progression (PD) was 94,141.8 CZK/3651.7 Euro (sunitinib: 11 months to PD, cost to PD 1,267,648.5 CZK/49,171.8 Euro; sorafenib: 8 months to PD, cost to PD 896,670.1 CZK / 34,781.6 Euro). The incremental cost-effectiveness ratio was 123,659.5 CZK / 4796.7 Euro per progression-free month in sunitinib vs sorafenib patients. The mean cost per month after PD was 45,767.0 CZK/1775.3 Euro with sequential therapy (sorafenib after sunitinib failure and vice-versa in more than half of patients) or best supportive care. 16 patients died during the study period with mean cost of 1,180,795.4CZK/45,802.8 Euro per 12 months (median between treatment initiation with sunitinib or sorafenib and death). 8 patients (26%) did not achieve progression (median progression-free survival to 09/2009: sunitinib 18 months, sorafenib 14 months).
The cost of medication made up more than 95% of total costs to PD and more than 90% after PD. The cost per progression-free month was 123,659.5 CZK/4796.7 Euro in mRCC patients treated with sunitinib vs sorafenib.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2010; 23(6):439-45.