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Kopeckova K.,Onkologicka klinika
Onkologie (Czech Republic) | Year: 2017

Despite the extensive possibilities of systemic treatment for advanced renal cell carcinoma have been still missing positive adjuvant trials. Several studies with immunotherapy based on interferon alfa or interleukin -2 failed. The adjuvant trials with TKI concluded with conflicting results. The ASSURE study compared sunitinib or sorafenib with placebo was not able to detect any difference in diseases free survival compared to placebo and was associated with high rate of toxicity and discontinuation of treatment. The adjuvant trial S-TRAC comparing sunitinib and placebo resulted in prolonged diseases free survival 6.8 years vs. 5.6 years. None of these trials incorporated a new validated genetic recurrence score to predict the risk of recurrence. The adjuvant systemic treatment for renal cell carcinoma is not recommended in the clinical daily practise today.


Buchler T.,Onkologicka klinika
Onkologie (Czech Republic) | Year: 2017

Renal cell carcinoma (RCC) has traditionally been considered an immunogenic malignancy. Despite this, the majority of existing immunotherapeutic strategies have brought only little benefit to patients with a generalized tumour. In some clinical settings, however, a novel generation of immunotherapeutic drugs, particularly those from the group of checkpoint inhibitors, has shown superiority over standard targeted therapy, while having relatively low toxicity.


Buchler T.,Onkologicka klinika
Onkologie (Czech Republic) | Year: 2016

Systemic treatment for bladder cancer is indicated in four clinical situations, including neoadjuvant therapy prior to radical cystectomy for muscle-invasive bladder cancer, adjuvant chemotherapy after cystectomy for muscle-invasive bladder cancer, as a part of bladder sparing protocols in concomitance with radiotherapy, and for treatment of advanced or metastatic disease. Chemotherapy regimens containing cisplatin are the basis of current systemic therapies for bladder cancer.


Motzer R.J.,Sloan Kettering Cancer Center | Hutson T.E.,Texas Oncology | Glen H.,Beatson West of Scotland Cancer Center | Michaelson M.D.,Massachusetts General Hospital | And 12 more authors.
The Lancet Oncology | Year: 2015

Background: Currently, metastatic renal cell carcinoma is treated with sequential single agents targeting VEGF or mTOR. Here, we aimed to assess lenvatinib, everolimus, or their combination as second-line treatment in patients with metastatic renal cell carcinoma. Methods: We did a randomised, phase 2, open-label, multicentre trial at 37 centres in five countries and enrolled patients with advanced or metastatic, clear-cell, renal cell carcinoma. We included patients who had received treatment with a VEGF-targeted therapy and progressed on or within 9 months of stopping that agent. Patients were randomised via an interactive voice response system in a 1:1:1 ratio to either lenvatinib (24 mg/day), everolimus (10 mg/day), or lenvatinib plus everolimus (18 mg/day and 5 mg/day, respectively) administered orally in continuous 28-day cycles until disease progression or unacceptable toxic effects. The randomisation procedure dynamically minimised imbalances between treatment groups for the stratification factors haemoglobin and corrected serum calcium. The primary objective was progression-free survival in the intention-to-treat population. This study is closed to enrolment but patients' treatment and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT01136733. Findings: Between March 16, 2012, and June 19, 2013, 153 patients were randomly allocated to receive either the combination of lenvatinib plus everolimus (n=51), single-agent lenvatinib (n=52), or single-agent everolimus (n=50). Lenvatinib plus everolimus significantly prolonged progression-free survival compared with everolimus alone (median 14·6 months [95% CI 5·9-20·1] vs 5·5 months [3·5-7·1]; hazard ratio [HR] 0·40, 95% CI 0·24-0·68; p=0·0005), but not compared with lenvatinib alone (7·4 months [95% CI 5·6-10·2]; HR 0·66, 95% CI 0·30-1·10; p=0·12). Single-agent lenvatinib significantly prolonged progression-free survival compared with everolimus alone (HR 0·61, 95% CI 0·38-0·98; p=0·048). Grade 3 and 4 events occurred in fewer patients allocated single-agent everolimus (25 [50%]) compared with those assigned lenvatinib alone (41 [79%]) or lenvatinib plus everolimus (36 [71%]). The most common grade 3 or 4 treatment-emergent adverse event in patients allocated lenvatinib plus everolimus was diarrhoea (ten [20%]), in those assigned single-agent lenvatinib it was proteinuria (ten [19%]), and in those assigned single-agent everolimus it was anaemia (six [12%]). Two deaths were deemed related to study drug, one cerebral haemorrhage in the lenvatinib plus everolimus group and one myocardial infarction with single-agent lenvatinib. Interpretation: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma. Funding: Eisai Inc. © 2015 Elsevier Ltd.


Targeted therapy is indicated for many types of solid malignancies, either in monotherapy or in combination with chemotherapy, hormonal therapy, or radiotherapy. The incorporation of targeted drugs into clinical algorithms has improved the prognosis of many cancers but also increased the risk of some less common adverse effects. Targeted therapy may increase haematological toxicity of chemotherapy and cause disruption of protective barriers or directly inhibit the function of immune cells. Routine prophylactic anti-infective therapy in patients treated with current targeted therapies for solid tumors is not recommended. Some targeted drugs, however, may predispose to specific infectious complications.


Tesarova P.,Onkologicka Klinika
Ceska a Slovenska Gastroenterologie a Hepatologie | Year: 2010

The advancement in the systemic treatment of hepatocellular carcinoma (HCC) has improved prospects for the overall survival rate in patients with the advanced form of the tumour. In this overview, the new targeted therapy is set in the context of both traditional and the latest therapeutical methods, which include - besides liver transplant, partial hepatectomy, radiofrequency ablation and alcoholization - also radiotherapy, immunotherapy, chemotherapy and biological therapy. Local therapy is usually preferred to systemic therapy. Patients for whom locoregional therapy is not suitable due to advanced disease can benefit from systemic therapy. The targeted therapy with sorafenib, a multiple tyrosine kinase inhibitor, which was proven in the SHARP study to produce a statistically significant improvement in the overall survival rate of patients with advanced HCC, has become a new standard in systemic therapy of advanced HCC. Sorafenib demonstrated high efficacy in monotherapy compared to the placebo and is the first and so far only drug which has significantly improved the overall survival rate in patients with HCC. Other biological drugs include bevacizumab, sunitinib and erlotinib. To conclude, current recommendations on HCC treatment are presented.


Petruzelka L.,Onkologicka Klinika
Vnitrni Lekarstvi | Year: 2011

Clinical use of targeted biological treatment was initiated in 1970s following a discovery of hormonal receptors and targeted clinical use of tamoxifen. Deeper understanding of molecular principles of the process of metastasizing and cell communication and signalling have contributed to the development of targeted molecular biological treatments based on direct impact on the key target structures of a tumour cell. Clinical effectiveness of targeted biological treatment has been shown in phase III clinical studies in advanced and metastasising solid tumours and importantly expanded our armamentarium of pharmacotherapeutic treatment options in breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, hepatocellular carcinoma and gastrointestinal stromal tumour. Full implementation of targeted therapy is precluded by a lack of reliable predictors of efficacy of a number of targeted drugs. Therefore, full identification of such predictors is a subject to intensive clinical research. At present, selection of biological treatment is based on morphological, immunohistochemical and partly also molecular profile of a tumour. The future of biological treatment lies in a selection that is based on full molecular characterization of the primary tumour as well as metastasis.


Tesarova P.,Onkologicka Klinika
Aktuality v Nefrologii | Year: 2015

The therapy of overlapping problems of anemia in chronic renal failure and anemia of chronic disease associated with malignancies is one of a series of border issues between the oncology and nephrology, which may be included in the issue onconephrology (acute and chronic renal failure in patients with malignant tumor, nephrotoxicity of anticancer therapy, paraneoplastic syndromes with a the kidney injury, the patients after nephrectomy for kidney cancer, antitumor treatment and replacement of kidney function, kidney transplant in patients in remission of malignancy, systemic treatment of cancer patiens after kidney transplantation, treatment of pain in patients with malignancy and chronic renal insufficiency). New recommendations for the optimal therapeutic approach in these situations should most likely be based on the results of recent clinical studies in onconephrology A meta-analysis of clinical and preclinical trials with ESA in cancer patiens not confirmed the negative impact of the ESA on the progression of a malignant tumor, but some of the individual trials have demonstrated a link between the administration of the ESA and the progression of the disease. For the safe and a sufficient effect of the treatment, it is necessary to adhere to the principles of the administration of ESA based on the recommendations of the ASCO/ASH, ESMO, EORTC rules.


Buchler T.,Onkologicka Klinika
Klinicka Onkologie | Year: 2015

Background: Renal cell carcinoma is characterised by chemo- and radioresistance. Although drugs targeting angiogenesis and intracellular signaling have become the mainstay of systemic therapy for renal cell carcinoma in the last decade, latest immunotherapeutic approaches have achieved promising results. Aim: To review the development of immunotherapy for renal cell carcinoma, especially the results of published studies using novel immunotherapeutic agents including checkpoint inhibitors. Results: It has long been known that nonspecific immunotherapy may result in long term complete remission in a small number of patients. Advances in immunology have led to the renewal of interest in the use of anticancer immunotherapy for metastatic renal cell carcinoma. Promising results in phase I and II studies have been achieved using monoclonal antibodies against PD-1 receptor and its ligand. Studies comparing immunotherapy to standard targeted therapies are ongoing.


In recent years, thanks to new advances in tumor immunology, immunotherapy became a part of intensive research as a novel strategy in cancer treatment. Sipuleucel-T is the first and only medicinal product approved by the regulatory agencies in the USA and Europe for the treatment of asymptomatic or minimal symptomatic castrate-refractory prostate cancer. It represents the first product of autologous cell therapy. This article gives a brief overview of new approaches in cancer immunotherapy in clinical development.

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