03/2019

03/2019 MUDr. Otakar Čapoun, Ph.D., FEBU
Metastatic prostate cancer has a significantly worse prognosis compared to localized or locally advanced disease. The first choice in most patients is androgen deprivation therapy, i.e. castration. The effect of docetaxel chemotherapy and novel hormonal agents (abiraterone, enzalutamide) was first demonstrated in the stage of castration resistance. Docetaxel has also been tested in combination with androgen deprivation therapy for newly diagnosed metastatic prostate cancer without prior castration. Significantly longer overall survival was achieved in the group of combined therapy. However, a significant effect was observed only in patients with high volume metastatic disease. Abiraterone has also been studied in combination with androgen deprivation therapy in the first line of therapy of high-risk metastatic hormone-sensitive prostate cancer. Again, overall survival was significantly longer for combined therapy. The safety profile of both docetaxel and abiraterone is favorable, but when choosing between these strategies, one must consider the general condition of the patient, his symptoms and comorbidities as well as his preferences.

03/2019 MUDr. Jana Katolická, Ph.D.
Immunotherapy is not used in routine clinical practice in the treatment of prostate cancer. Traditional endpoints used to evaluate chemotherapy may not assess accurately the clinical benefit from immune therapies. The mechanism of action of most immune therapies is not directly cytotoxic. The higher clinical benefit was found in favorable subgroups with a lower tumor burden and a less immunosuppressive tumor microenvironment.

03/2019 MUDr. Jindřich Kopecký, Ph.D.
In the last decade, we are witnesses of great development and improvement in renal cancer therapy. Based on better understanding of the mechanisms of pathogenesis and the improvement in immunotherapy, we are able to reach long-term responses. Currently, it is still not clear, if there is a choice of, which drug to use. We do not always have head to head comparisons of drugs. In our conditions is this issue partially artificially simplified due to reimbursement. The following article discusses the current status, advantages and disadvantages of immunotherapy and targeted therapy in renal cancer.

03/2019 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Jiří Baroš; MUDr. Vladimír Šámal
Renal cell cancer accounts 2-3 % of all cases of malignancy. Sunitinib and Pazopanib have so far been standard in first line treatment of metastatic renal cell cancer. In this review we discuss current first-line treatment options as new tyrosine kinase inhibitor cabozantinib, the new combination of immunotherapy (nivolumab plus ipilimumab), and combination of immunotherapy and tyrosine kinase inhibitor. With the growing therapeutic options, identification of new biomarkers will be crucial for optimizing first-line selection.

03/2019 MUDr. Kristýna Divišová; MUDr. Jana Katolická, Ph.D.; MUDr. Milan Kohoutek
Cisplatin-based chemotherapy is the standard first-line treatment in advanced urothelial cancers. However, more than 50 % of patients are not eligible for cisplatin. Urothelial cancer patients are of higher median age and often present with organ impairment and comorbidities. In frail patients, recommended treatment options include carboplatin or gemcitabine monotherapy, or GCa or imunotherapy if possible.

03/2019 MUDr. Robert Novák; MUDr. Jana Katolická, Ph.D.; MUDr. Jiří Vašina
In our case report, we present a case of a patient initially with locally-regionally advanced prostate cancer. The complete remission was achieved after sequential treatment of docetaxel-cabazitaxel-enzalutamide, with maintaining good quality of life.

03/2019 MUDr. Leona Koubková
Immunotherapy has already become an integral part of advanced non-small cell lung cancer treatment. The results of a number of studies have shown an improvement in the overall survival time, which is often long-lasting at a very good quality of life for patients. Recent studies have also been conducted at lower stages of non-small cell lung cancer or in post-operative adjuvant mode. The results of studies in advanced small cell lung cancer are also promising, with no progress in treatment for decades. Durvalumab is an anti PD-L1 monoclonal antibody that is approved by the Food and Drug Administration and European Medicines Agency based on the results of the PACIFIC study, for the treatment of patients with non-recurrent non-small cell lung cancer stage III, whose disease did not progress after chemoradiotherapy.

03/2019 MUDr. Eugen Kubala
Dissatisfaction with the current state of the complex metastatic colorectal cancer treatment leads to a deeper analysis of the right choice of consecutive treatment line. Metastatic colorectal cancer remains incurable in most cases. We have a variety of cytostatics and biological treatments available. The right choice for the 1^st line of treatment, which is crucial for the outcome of the whole treatment, seems to be crucial. The selection is based on knowledge of biological markers of RAS and BRAF and clinical factors. The result of successive lines depends on choosing the correct 1^st line. In the 2^nd line, anti-angiogenic agents (bevacizumab, ramucirumab and aflibercept) were used. Epidermal growth factor receptor (EGFR) inhibitors do not increase 2^nd-line survival. The 3^rd line is dependent on the molecular examination of the tumor. Knowing the status of the RAS BRAF mutation determines whether we use anti EGFR antibodies or BRAF and MEK inhibitors. The state of microsatellite stability is critical to the use of immunotherapy (pembrolizumab, nivolumab, and ipilimumab. Proper understanding of the mechanisms of selection of sequential therapy and its de-escalation and re-escalation may lead to prolonged positive treatment outcomes. A significant difference between progression to full treatment or de-escalated treatment, the latter allowing reuse of the substance that was used at the start of treatment, knowledge of the molecular profile of tumors that appears to be essential in the choice of treatment should contribute to the correct management of treatment. In the 1^st, 2^nd and 3^rd line of therapy, the selective pressure of treatment on cell subpopulations of the tumor limits the success of the next treatment line.

03/2019 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Jiří Bartoš; doc. MUDr. Tomáš Jirásek, Ph.D.
The neoadjuvant chemoradiotherapy with following total mesorectal excision is a current standard of the treatment of locally advanced rectal adenocarcinoma. In addition to traditional prognostic factors (as clinical stage, surgery radicality, etc.), new biomarkers are also being sought with the aim to optimize the treatment of this malignancy. One of these biomarkers is detection of PD-L1 on the tumor cell surface. The aim of this paper is to determinate the prognostic influence of PD-L1 expression changes in patients with locally advanced rectal cancer treated by neoadjuvant chemoradiotherapy. The combination of PD-1/PD-L1 inhibitors has not gained an acceptance as a new standard of treatment of these malignancies.

03/2019 MUDr. Aneta Rajdová; MUDr. Jana Raputová; MUDr. Eva Vlčková, Ph.D.
Chemotherapy-induced peripheral neuropathy (CIPN) is frequent adverse effect of anticancer treatment. It can severely affect the quality of life of cancer survivors, and lead to dose reduction or discontinuation of the treatment. Clinical symptoms completely or partially resolve after cessation of chemotherapy in most of the patients. However, in subset of them could be irreversible. The most neurotoxic agents are the platinum-based antineoplastic drugs, the vinca alkaloids, the taxanes, the proteasome inhibitors (bortezomib) and thalidomide. CIPN predominantly affects sensory neurons, less frequently autonomic or motor neurons which is manifested for instance by orthostatic hypotension or muscle weakness. Administration of neurotoxic chemotherapy should be carefully considered regarding protentional existence of neuropathy in high-risk patients to prevent CIPN development. If the polyneuropathy occurs during anticancer treatment, dose reduction or change of antineoplastic agent can prevent further worsening of the peripheral nerve impairment.

03/2019 MUDr. Karolína Hovorková
Alopecia is one of the most common and unpleasant side effects of chemotherapy when treating solid tumors. So far, the only method preventing/reducing chemotherapy induced hair loss is hair scalp cooling system DigniCap®. The cooling system has been used at our clinic since 2014. Producer declared effects correspond with our experience.

03/2019 Doc. MUDr. Alexandr Poprach, Ph.D.; MUDr. Radek Lakomý, Ph.D.
The patients with metastatic malignant melanoma had a very poor prognosis in the past, chemotherapy was highly palliative and not so efficient. The use of checkpoint inhibitors (such as the anti-PD-1 antibody nivolumab) changed the prognosis and treatment results. The probability of 5-years overall survival is approximately 50 % by using the combination of anti-CTLA-4 and anti-PD-1 antibodies. However, the use of checkpoint inhibitors could cause the immune-related side effects that may be fatal. Herein we introduce a story of our patient with metastatic renal cell carcinoma with Guillain-Barré syndrome after the first dose of nivolumab. We had treated him with combined immunosuppressive therapy, plasmapheresis and intensive supportive care but he died of this complication in the end. The onset of first signs of this side effect was 5 days after the first dose of nivolumab which is remarkable.

03/2019 MUDr. Michal Vočka
Trifluridine/tipiracil (Lonsurf), combination of trifluridine (analogue of thymidine-nucleoside) and tipiracil (thymidine phosphorylase inhibitor involved in thymidine catabolism), is one of the options for a higher-line treatment in metastatic colorectal cancer patients. The case report describes the use of this drug in the fourth line, when the disease was stabilized for 17 months without any significant side effects associated with the therapy.