Assessment of delta-9-tetrahydrocannabinol (THC) in saliva and blood after oral administration of medical cannabis with respect to its effect on driving abilities.

Medical cannabis has recently been legalized in many countries, and it is currently prescribed with increasing frequency, particularly for treatment of chronic pain resistant to conventional therapy. The psychoactive substance delta-9-tetrahydro-cannabinol (THC) contained in cannabis may affect driving abilities. Therefore, the aims of this study (open-label, monocentric, nonrandomized) were to evaluate blood and saliva concentrations of THC after oral administration of medical cannabis and to assess the time needed for THC levels to decline below a value ensuring legal driving. The study involved 20 patients with documented chronic pain using long-term medical cannabis therapy. They were divided into two groups and treated with two different doses of cannabis in the form of gelatin capsules (62.5 mg or 125 mg). In all patients, the amount of THC was assessed in saliva and in blood at pre-defined time intervals before and after administration. THC levels in saliva were detected at zero in all subjects following administration of both doses at all-time intervals after administration. Assessment of THC levels in blood, however, showed positive findings in one subject 9 h after administration of the lower dose and in one patient who had been given a higher dose 7 h after administration. Our finding suggested that for an unaffected ability to drive, at least 9-10 h should elapse from the last cannabis use.

Anisocoria as a side effect of paclitaxel treatment.

BACKGROUND: Paclitaxel is one of the most common cytostatics used in oncology; it is part of the therapeutic protocols of many malignancies. One of its most common side effects is peripheral neuropathy. This symptomatology often leads to a reduction in the dose intensity of chemotherapeutic drugs or to early discontinuation of the treatment. CASE: In our case report, we describe a rare case of paclitaxel-induced anisocoria in a young woman with breast cancer. CONCLUSION: Ocular side effects related to taxanes are rare, with an estimated frequency of about 1%. In addition to relatively frequent obstruction of the nasolacrimal duct, the cystoid macular edema or ischemic retinopathy have been reported. However, in most cases paclitaxel-induced ocular side effects, there is no need to reduce or discontinue therapy. However, the collaboration of an oncologist with an experienced and trained ophthalmologist is essential.

Investigator Initiated Clinical Trials (IICTs): A Systematic Search in Registries to Compare the Czech Republic and Portugal in Terms of Funding Policies and Scientific Outcomes.

OBJECTIVES: Clinical trials provide one of the highest levels of evidence to support medical practice. Investigator initiated clinical trials (IICTs) answer relevant questions in clinical practice that may not be addressed by industry. For the first time, two European Countries are compared in terms of IICTs, respective funders and publications, envisaging to inspire others to use similar indicators to assess clinical research outcomes. METHODS: A retrospective systematic search of registered IICTs from 2004 to 2017, using four clinical trials registries was carried out in two European countries with similar population, GDP, HDI and medical schools but with different governmental models to fund clinical research. Each IICT was screened for sponsors, funders, type of intervention and associated publications, once completed. RESULTS: IICTs involving the Czech Republic and Portugal were n = 439 (42% with hospitals as sponsors) and n = 328 (47% with universities as sponsors), respectively. The Czech Republic and Portuguese funding agencies supported respectively 61 and 27 IICTs. Among these, trials with medicinal products represent 52% in Czech Republic and 4% in Portugal. In the first, a higher percentage of IICTs' publications in high impact factor journals with national investigators as authors was observed, when compared to Portugal (75% vs 15%). CONCLUSION: The better performance in clinical research by Czech Republic might be related to the existence of specific and periodic funding for clinical research, although further data are still needed to confirm this relationship. In upcoming years, the indicators used herein might be useful to tracking clinical research outcomes in these and other European countries.

The Current Status of European and National Financial Sources for Clinical Research and Their Impact on Paediatric Non-commercial Clinical Trials: A Case Study of the Czech Republic.

INTRODUCTION: Paediatric non-commercial interventional clinical trials (NICTs) are crucial for healthcare provision. In spite of the fact that current regulations and initiatives try to enhance the quantity and quality of paediatric NICTs, there are still shortcomings that need to be addressed in order to accelerate the conduct of relevant clinical trials in children. To improve the current landscape of paediatric clinical research, it is necessary to identify and analyse the main trends and shortcomings, along with their impact on national performance in paediatric NICTs and this is the aim of this work. METHOD: A retrospective systematic search of paediatric NICTs was performed on four international clinical trials registries. Entries were filtered by date from 01/01/2004 to 31/12/2017. Each identified paediatric NICT was screened and analysed for sponsors, funders, type of intervention, therapeutic area, design characteristics and associated publications. RESULTS: The search identified 439 unique NICTs. When stratifying the trials by enrolment ages, 86 trials were found involving the paediatric population. Most trials investigated the use of medicinal products and were focused on cancer or cardiovascular diseases. The most common sources of the funding were non-profit organizations. Furthermore, from the total number of completed trials, only half of them already published their results. CONCLUSION: The main shortcomings-specifically, ethical, methodological and, in particular, economic obstacles were identified. There is a continual need for greater support and collaboration between all major stakeholders including health policymakers, grant agencies, research institutions, pharmaceutical industries and healthcare providers at the national and international level.

European survey on national training activities in clinical research.

BACKGROUND: Investigator-initiated clinical studies (IITs) are crucial to generate reliable evidence that answers questions of day-to-day clinical practice. Many challenges make IITs a complex endeavour, for example, IITs often need to be multinational in order to recruit a sufficient number of patients. Recent studies highlighted that well-trained study personnel are a major factor to conduct such complex IITs successfully. As of today, however, no overview of the European training activities, requirements and career options for clinical study personnel exists. METHODS: To fill this knowledge gap, a survey was performed in all 11 member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardised questionnaire. Three rounds of data collection were performed to maximize completeness and comparability of the received answers. The survey aimed to describe the landscape of academic training opportunities, to facilitate the exchange of expertise and experience among countries and to identify new fields of action. RESULTS: The survey found that training for Good Clinical Practice (GCP) and investigator training is offered in all but one country. A specific training for study nurses or study coordinators is also either provided or planned in ten out of eleven countries. A majority of countries train in monitoring and clinical pharmacovigilance and offer specific training for principal investigators but only few countries also train operators of clinical research organisations (CRO) or provide training for methodology and quality management systems (QMS). Minimal requirements for study-specific functions cover GCP in ten countries. Only three countries issued no requirements or recommendations regarding the continuous training of study personnel. Yet, only four countries developed a national strategy for training in clinical research and the career options for clinical researchers are still limited in the majority of countries. CONCLUSIONS: There is a substantial and impressive investment in training and education of clinical research in the individual ECRIN countries. But so far, a systematic approach for (top-down) strategic and overarching considerations and cross-network exchange is missing. Exchange of available curricula and sets of core competencies between countries could be a starting point for improving the situation.

The safety of therapeutic monoclonal antibodies: implications for cancer therapy including immuno-checkpoint inhibitors.

Monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both hematologic malignancies and solid tumors. In addition to targeting cancer antigens antibodies can also modulate immunological pathways that are critical to immune surveillance. Antibody therapy directed against several negative immunologic regulators (checkpoints) is demonstrating significant success in the past few years. Immune checkpoint inhibitors, ipilimumab, pembrolizumab and nivolumab, have shown significant clinical benefit in several malignancies and are already approved for advanced melanoma and squamous NSCLC. Based on their mechanism of action, these agents can exert toxicities that are unlike conventional cytotoxic chemotherapy, whose nature is close to autoimmune diseases - immune related adverse events (irAEs). In this review we focus on the spectrum of irAEs associated with immune checkpoint antibodies, discussing the pharmacological treatment strategy and possible clinical impact.

Systemic administration of miRNA mimics by liposomal delivery system in animal model of colorectal carcinoma.

MiRNAs are important regulators of gene expression and changes in their levels are linked with various pathological states, including solid tumors. MiR-215 has been identified as a tumor suppressor in colorectal cancer (CRC). Following our previous in vitro and in vivo experiments, the aim of this project was to study the possibility of increasing the levels of miR-215 in tumor cells by systemic administration of miRNA mimics in liposomal delivery system in vivo. By subcutaneous xenotransplantation of human cancer cells to NSG mice, CRC model was established. The treatment (miR-215 mimics in liposomes [20 and 40 microg/mouse], control oligonucleotide in liposomes, or saline) was administered repeatedly by i.v. injection via tail-vein. Animals were sacrificed, tumor were dissected and measured by a caliper. Expression of miR-215 in tumors, lungs and liver was quantified by RT-PCR. There was no significant differences in tumor volume and miR-215 expression between all three treatment groups. Therefore, the decrease in tumor volume was not achieved. By comparing the levels of miR-215 in lungs, liver and tumors after the treatment, we suggest that the liposomes are accumulated in the lungs and do not concentrate sufficiently in the tumor site to exert significant tumor-suppressive effect.

[Non-Small Cell Lung Cancer - from Immunobiology to Immunotherapy]. / Nemalobunecný karcinom plic - od imunobiologie k imunoterapii.

BACKGROUND: The treatment of early or locally advanced stages of non-small cell lung cancer (NSCLC) is based on surgical resection or radiotherapy. Metastatic disease is always incurable, treatment is palliative, systemic based on chemotherapy or target therapy. NSCLC is the most common cause of cancer-related death worldwide, and new therapeutic approaches are needed. Based on the emerging data on the role of immune system in shaping of tumor outbreak and outcome, immunotherapy is currently in the center of interest of cancer research and therapy of solid cancers including NSCLC. Various anti-cancer vaccination approaches and antigen-independent immunomodulatory drugs are being developed and trialed. The most advanced in terms of approaching clinical practice are the so-called checkpoint inhibitors blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed cell death of the protein and its ligand (PD-1, PD-L1). Beside innovative drug development, the field of cancer immunotherapy focuses on the identification and clinical application of effective biomarkers of clinical efficacy and on the evaluation of combinations of immunotherapeutic drugs or with classical anti-cancer approaches, such as chemotherapy, radiotherapy or with targeted therapy. AIM: In this review, we summarize basic principles of immnobiology of NSCLC in the context of innovative immunotherapeutics, strategy and phase III results of anti-cancer vaccines in NSCLC, results of NSCLC treatment with checkpoint inhibitors, and current challenges in immunotherapy of lung cancers.Key words: non-small cell lung cancer - immunotherapy - cancer vaccines - drug response biomarkersThis work was supported by MEYS - NPS I - LO1413.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 recommendation for biomedical papers.Submitted: 10. 6. 2016Accepted: 16. 6. 2016.

[Current Progresses in Developing PET Radiopharmaceuticals for Patients in the Czech Republic]. / Pokroky ve vývoji PET radiofarmak pro pacienty v Ceské republice.

BACKGROUND: In Masaryk Memorial Cancer Institute (MMCI), there is a long-running intensive joint effort of the RECAMO project and commercial entities, involving mainly clinical evaluations of state-of-the-art PET radiopharmaceuticals leading to their future availability for Czech physicians and their patients. Recently, the PET tracers [11C]methionine and [18F]fluorocholine, among others, were developed in this cooperation, both of them tracers with high importance for oncologic positron emission tomography diagnostics. [11C]methionine, labeled by carbon-11 with a half-life of 20 min, is a proteosynthesis marker used primarily for brain tumor visualization, whereas [18F]fluorocholine, labeled by fluorine-18 with a half-life of 109 min, is a marker of synthesis of cellular membranes and cell proliferation, its primary use being PET diagnostics of prostate carcinoma. AIM: The results of clinical evaluations of both PET radiopharmaceuticals, performed on the basis of parameters agreed and approved beforehand in cooperation of MMCI, RECAMO and the manufacturer of said radiopharmaceuticals, aimed to prove the efficiency and suitability of both compounds for oncologic PET diagnostics for said tumors. In both cases, the radiopharmaceuticals were evaluated in regard to their major use. CONCLUSION: The obtained results prove the benefits and efficiency of both compounds in PET diagnostics of respective tumors. The results, in the form of clinical evaluation reports, will be used as part of the documentation required for marketing authorization of these compounds for use in the Czech Republic.Key words: positron emission tomography - radiopharmaceuticals - L-methyl-11C-methionine - 18F-fluorocholineThis work was supported by the project MEYS - NPS I - LO1413.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 recommendation for biomedical papers.Submitted: 10. 6. 2016Accepted: 17. 6. 2016.

[Circulating Levels of Estradiol in Breast Cancer Patients Treated with Aromatase Inhibitors and Their Clinical Implications]. / Sledování cirkulujících hladin estradiolu u pacientek s karcinomem prsu lécených inhibitory aromatázy - prínos v klinické praxi.

Adjuvant treatment with aromatase inhibitors improves outcomes in postmenopausal women with hormone-sensitive early breast cancer; however, they should not be used in premenopausal women. Menopausal status is the most important factor in the choice of the hormonal treatment. There is no direct correlation between amenorrhea and ovarian function, as even the patients with amenorrhea may present with premenopausal plasma estradiol levels. The evaluation of hormonal status becomes more complicated in patients taking tamoxifen, which might lead to further increase of plasma estradiol levels. Therefore, its evaluation before and during the treatment with aromatase inhibitors is clinically important. There is a considerable caution needed when indicating aromatase inhibitors in patients with menopause caused by previous adjuvant chemotherapy, while recovery of ovarian function may appear after a certain period. This could take from 4 to 59 months (12 months on average) and it might not be accompanied by menses. This happens typically in women younger than 40 years, who should, therefore, not be treated by aromatase inhibitors alone. This supports the notion that monitoring of plasma estradiol levels is crucial in women from 40 to 50 years of age, especially before the start of aromatase inhibitors treatment.Key words: breast cancer - premenopause - postmenopause - perimenopause - estradiol - aromatase inhibitorsThis work was supported by MEYS - NPS I - LO1413 for RECAMO.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 recommendation for biomedical papers.Submitted: 18. 2. 2016Accepted: 29. 6. 2016.

Time-course pattern of blood 25-hydroxycholecalciferol is a significant predictor of survival outcome in metastatic colorectal cancer: a clinical practice-based study.

Vitamin D deficiency has been implicated in the epidemiology of common malignancies including colorectal cancer. We studied consecutive blood levels of 25-hydroxycholecalciferol (25-OHD) in relation to other clinical and laboratory variables in metastatic colorectal cancer patients to ascertain whether their variations may be prognostic or predictive parameters of survival outcomes. Eighty four patients treated with first-line oxaliplatin-based chemotherapy with or without bevacizumab were included. The patients were enrolled on the intent-to-treat basis considering their performance status, comorbidities and laboratory parameters to be medically apt for intensive chemotherapy. Overall survival and progression-free survival were selected as the primary outcomes. Progression free survival and overall survival medians were 15.4 months and 41.2 months, respectively. The cut-off levels of 40 nmol/l for 25-OHD and 11 µg/l for first CEA were identified to be clinical decision levels stratifying patients to the respective prognostic groups. We found that the most consistent outcome predictors were i) any patient surgery, ii) CEA and, independently, iii) time-related blood levels of 25-OHD. We confirmed fundamental and consistent vitamin D deficiency in metastatic colorectal cancer. We demonstrated that all patients with at least one blood level above 40 nmol/l versus all below this cut-off showed profound differences in their disease outcomes. The primary disease stage or time to metastatic stage did not influence the predictive power of blood 25-OHD levels, implying that the time-course pattern of 25-OHD but not the first single measurement may be an independent prognostic factor.

[Potential clinical benefit of therapeutic drug monitoring of imatinib in oncology]. / Mozný klinický prínos terapeutického monitorování hladin imatinibu v onkologii.

Imatinib mesylate is a competitive inhibitor of BCR/ ABL tyrosine kinase and inhibits also several receptor tyrosin kinases. Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) -  positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. The drug is metabolized by cytochrome P450, and there are many clinically important pharmacokinetic drug-drug interactions described in the literature. Frequent polypharmacy in oncological patients increases probability of such interactions, and also adherence may play its role during longterm treatment. Fixed dosing therapeutic regimens fail to respect known interindividual variability in pharmacokinetics of the drug and thus, some patients may not achieve sufficient plasma concentrations. Based on current evidence, there seems to be a relationship between plasma concentration and clinical response to imatinib. Therefore, imatinib appears to be suitable candidate for therapeutic drug monitoring. Here, we present an overview of pharmacokinetics, drug-drug interactions and current knowledge and suggestions on therapeutic drug monitor-ing of imatinib, its potential benefits and limitations.

Successful use of metronomic vinblastine and fluorothymidine pet imaging for the management of intramedullary spinal cord anaplastic oligoastrocytoma in a child.

BACKGROUND: 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. OBSERVATION: 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. CONCLUSIONS: Metronomic treatment guided by positron-emission tomography could be a reasonable option in some high-risk pediatric tumours.

[The cost study of first- line treatment of metastatic colorectal carcinoma with bevacizumab- containing regimen in the Czech Republic]. / Analýza nákladu na 1. linii lécby metastatického kolorektálního karcinomu pri podání rezimu s bevacizumabem -  data z reálné klinické praxe v Ceské republice.

BACKGROUND: Bevacizumab, a humanized monoclonal IgG antibody against the vascular endothelial growth factor (VEGF), is reimbursed in combination with chemotherapy for the first and subsequent line 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. PATIENTS AND METHODS: A total of 218 patients were included in our analysis. Cost data (examination, medication, hospitalization) were collected since the initiation of bevacizumab treatment to any tumor response (RECIST criteria: complete response -  CR, partial response -  PR, stable disease -  SD, progressive disease -  PD) and/ or to death. Minimal followup for all patients was 28 months. Costs were valued in Czech crowns (CZK) and converted to EUR (1€ = 25.14 CZK). RESULTS: PD was recorded in 194 patients (89% of patients). The mean cost of treatment to PD (median TTP 9.1 months) was 1,002,076.30 CZK (39,859.84 EUR). The majority of costs to PD was made by medication -  917,048.60 CZK (36,477.67 EUR) per patient. The mean cost to response PR, CR or SD was 1,105,823.10 CZK (43,986.60 EUR) after median 9.8 months of treatment (recorded for 21 patients), medication formed 1,023,827.70 CZK (40,725.05 EUR). During the study, 170 patients (78%) died. The mean of the total costs since initiation of treatment to death (median OS 18.8 months) was 1,338,874.20 CZK (53,256.70 EUR) -  out of that, medication was 1,184,251.10 CZK (47,106.25 EUR) per patient. CONCLUSION: Targeted bio-logical therapy is the largest part of the costs of mCRC therapy. Cost of bevacizumab made up to 69% of costs to PD -  687,608.20 CZK ( 27,351.20 EUR ) per patient. The majority of the total cost was formed by targeted drug therapy (bevacizumab in 1st line therapy, cetuximab and panitumumab in 2nd and 3rd line therapy); 58% of total costs since initiation of treatment to death -  778,233.80 CZK (30,956 EUR) per patient.

[Vitamin D as an important steroid hormone in breast cancer]. / Vitamin D jako významný steroidní hormon u karcinomu prsu.

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.

Metronomic chemotherapy with the COMBAT regimen in advanced pediatric malignancies: a multicenter experience.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

NKT-like cells are expanded in solid tumour patients.

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.

Phase I trial in oncology--theory and practice.

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.

[Economic evaluation of targeted biologic therapy in metastatic renal cell carcinoma]. / Analýza nákladu na cílenou biologickou lécbu pacientu s metastatickým karcinomem ledviny.

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.