Selected articles

Obinutuzumab in the treatment of patients with chronic lymphocytic leukemia and follicular lymphoma

03/2017 MUDr. Jana Zuchnická, MUDr. Jana Fečková Mihályová, MUDr. Juraj Ďuraš, prof. MUDr. Roman Hájek, CSc.
Monoclonal antibodies are used in the treatment of chronic lymphocytic leukemia and follicular lymphoma especially in combination with chemotherapy. The introduction of rituximab into clinical practice meant a real turning point, it changed medical procedures and the results of the treatment of both diseases. As of recently new monoclonal antibodies are being introduced into clinical practice which are being developed to enhance the antitumor effect. One of them is a humanized monoclonal antibody obinutuzumab. Obinutuzumab combined with chlorambucil is in the Czech Republic approved for the treatment of chronic lymphocytic leukemia in previously untreated patients with multiple comorbidities, who can't undergo fludarabin based treatment. In follicular lymphoma the indication of using obinutuzumab in combination with bendamustine is used for treating patients with rituximab refractory follicular lymphoma, we refer to the current summary of product characteristics. The use of obinutuzumab for patients with follicular lymphoma in the Czech Republic is still bound to being approved by the payer according to §16 of Act No. 48/1997 Coll.
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Immune‑related adverse events

02/2017 MUDr. Aneta Kyllarová, MUDr. Ondřej Kubeček, MUDr. Jindřich Kopecký, Ph.D.
Immunotherapy has gradually become a part of standard treatment of selected solid tumours since 2011. The spectrum of malignancies suitable for this treatment modality has been increasing since then. Consequently, the amount of patients treated with immunotherapy has been rising. Despite undeniable efficacy of this modality, we are facing a new spectrum of adverse effect distinct from conventional therapies (radiotherapy, chemotherapy). The aim of this article is to provide a brief review on the most common adverse effects of immunotherapy and their management. We aim to provide physicians, who do not routinely deal with these drugs, with some basic information, so that they are able to manage some minor toxicities or refer the patients to appropriate cancer centre.
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Immunotherapy of malignant melanoma

02/2017 MUDr. Alexandr Poprach, Ph.D., MUDr. Radek Lakomý, Ph.D.
Metastatic and/or locally advanced inoperable melanoma is still an incurable disease. On the other hand the progress in the new treatment's options causes significant prolongation of time to progression and overall survival. Treatment of metastatic melanoma could be divided into three goups. Checkpoint inhibitors - anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and anti-PD-1 (programmed death 1) or PD-L1 inhibitors - are in the first group, BRAF and MEK inhibitors belong to the second group. Cytostatics are in the last group. We will point out drugs from the first group in this review and the results of the actual studies will be mentioned.
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News in the adenocarcinoma of oesophagus and gastric adenocarcinoma treatment – present and future

02/2017 MUDr. Radka Obermannová, Ph.D.
Adenocarcinoma of distal oesophagus and gastric adenocarcinoma still have a poor clinical outcome. In locally advanced adenocarcinoma multimodal treatment has reached maximum of median overall survival. New molecular predictors defined recently by The Cancer Genome Atlas offer an opportunity of patient stratification to optimal treatment approach. PET/CT is a valuable method providing earlier identification of non-responders and enabling a well-timed change of ineffective treatment. Metastatic gastric cancer is very heterogeneous disease. Trastuzumab is the only clinically valid targeted therapy with a known molecular predictor. Antiangiogenic treatment is a standard of care in the second line treatment. Despite promising phase I/II clinical trials results, several phase III studies assessing receptor tyrosine kinase-related signaling pathways such as epidermal growth factor receptor, hepatocyte growth factor receptor (MET/HGF) or mammalian target of rapamycine receptor (mTOR) failed. Novel treatment targets include activation of immune response by PD-1/PD-L1 checkpoint inhibitors, inhibition of cancer stemness-related signaling pathways like STAT3, targeting DNA damage repair, stroma modification by matrix metalloproteinase-9 inhibition and Claudin-18.2, a tight junction protein antibody.
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PARP inhibitors in the treatment of ovarian cancer

02/2017 MUDr. Libor Ševčík, Ph.D.
Ovarian cancer is among gynecological tumors the most common cause of death and the fifth in deaths among oncological diseases. In the last decade there have been significant advances in genomic mapping of tumor cells and in the knowledge of molecular mechanisms in the pathogenesis of ovarian cancer. Targeted molecular therapy starts to apply in addition to cytotoxic chemotherapy. Widely researched and promising possibility of targeted treatment of ovarian cancer are PARP inhibitors olaparib, veliparib, niraparib, rucaparib and talazoparib that are examined in monotherapy and in combination with other molecules as potential amplifiers or cytotoxic damage during chemotherapy or radiation treatment. Poly(ADP-ribose)-polymerase (PARP) inhibitors cause targeted tumour cell death in homologous recombination (HR)-deficient cancers, including gene BRCA1, BRCA2 mutated tumours, by exploiting synthetic lethality. Among the five key PARP inhibitors currently in clinical development, olaparib has undergone the most extensive clinical investigation. PARP inhibitors have demonstrated durable antitumour activity in BRCA1/2 mutated advanced ovarian cancer as a single agent in the treatment and maintenance setting, particularly in platinum sensitive disease. Current research is extending the use of PARP inhibitors beyond BRCA1/2 mutations to other sensitising molecular defects that result in HR-deficient cancer.
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Eribulin – the indications and clinical results

02/2017 MUDr. Zuzana Donátová, MUDr. Drahomíra Kordíková, prof. MUDr. Jitka Abrahámová, DrSc.
Breast cancer in metastatic stage is considered as incurable disease. About 20% of all patients have distant metastases. The offer of new cytotoxic and biological agents caused prolongation of the overall survival in patients with metastatic disease. Eribulin is considered as the new effective cytotoxic agent for pre-treated patients with locally recurrent and metastatic breast cancer. Continuous research of its use was followed with extension of the indication in treatment of liposarcoma.
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Palbociclib in the treatment of advanced and/or metastatic hormone‑sensitive HER2‑negative breast cancer

02/2017 MUDr. Tomáš Svoboda, Ph.D.
Recently, we have the possibility to use in clinical practice a new targeted drug – palbociclib in the treatment of endocrine receptor positive, HER2 negative breast cancer. In the first line setting of treatment advanced/metastatic disease it is combined with letrozole and in the second line with fulvestrant. Cyclin dependent kinases 4 and 6 (CDK4/6) blockade inhibit the cell cycle progression in G1 phase and is associated with tumor cells proliferation prevention. The drug obtained a very high degree of recommendation and is a part of international guidelines.
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Optimal treatment approaches for patients with myelodysplastic syndrome

02/2017 MUDr. Petra Richterová, MUDr. Zdeněk Kořistek, Ph.D., MUDr. Lukáš Stejskal, prof. MUDr. Roman Hájek, CSc.
Myelodysplastic syndrome is a clonal disorder of the bone marrow caused by damage to the genetic information myeloid stem cell. It represents a heterogeneous group of disorders characterized by ineffective hematopoiesis with dysplasia of one or more myeloid lineage leading to cytopenia (or cytopenias) and the high incidence of progression to acute myeloid leukemia (about 1/3 cases). The blood count is most prevalently represented by anemia alone, in combination with thrombocytopenia or leucopenia, neutropenia. Clinical symptoms are consistent with the type and depth of the cytopenia – anemic syndrome, bleeding manifestation from thrombocytopenia or infectious complications in neutropenic patients. Myelodysplastic syndrome is a disease occurring almost solely in patients of older age (most frequent occurrence between 65–70 years), with an incidence of 3–5 new cases per 100,000 population per year. The incidence of myelodysplastic syndrome increases with age rapidly and in a group of people over 70 years amounts to 20 to 40 new cases per 100,000 inhabitants. Myelodysplastic syndrome is diagnosed as in the case of primary – unknown etiology, or secondary – often after chemotherapy or radiotherapy for an other cancer or after exposure to a known toxic agent.
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Osimertinib – a new oral third‑generation EGFR TKI

02/2017 MUDr. Leona Koubková
Non-small cell lung cancer (NSCLC) is a disease with a poor prognosis. Today we know that it involves a genetically distinct group of tumors. And of such genetic diversity leads to the tendency of individualized treatments based on the predictive factors that predict the efficacy of treatment. One of the predictive factors in NSCLC are mutations of the epidermal growth factor receptor (EGFR), in which case is indicated treatment EGFR tyrosine kinase inhibitors (TKI). Even if this treatment, we have to calculate with the formation of resistance. The mechanisms of its formation are different, most (up 60%), it is the T790M mutation at exon 20. In 11/2015 FDA and 2/2016 EMA approved EGFR TKI 3rd generation osimertinib to treat patients with locally advanced or metastatic NSCLC T790M mutation of EGFR.
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Pixantrone in the treatment of non‑Hodgkin lymphoma

02/2017 MUDr. Juraj Ďuraš, MUDr. Michal Kaščák, MUDr. Milan Navrátil, prof. MUDr. Roman Hájek, CSc.
Pixantrone is a novel aza-anthracenedione developed with aim of reducing cardiac toxicity whilst preserving the efficacy of anthracyclines. Pixantrone acts as an intercalating and an alkylating agent and weak topoisomerase II inhibitor. Unlike anthracycline pixantrone has reduced potential for the production of oxygen free radicals, which are probably the main factor of anthracycline’s cardiotoxicity. The maximum tolerated dose identified in the phase I study in relapsed and refractory aggressive non-Hodgkin’s lymphoma was 56 mg/m2 i.v. day 1, 8 and 15 in a 28day cycle. In Phase II and III was observed overall response in 27–40 %, complete remission in approximately 15 % of patients. In a randomized phase III study PIX 301 chieved overall response rate (40 %), complete or unconfirmed complete remission (24 %) and median time to progression (5,3 months) in the pixantrone arm was significantly higher than in the arm with single agent investigator choice. The main side effect of drug is haematotoxicity, primarily neutropenia. The risk of cardiotoxicity is not completely eliminated, but unlike in anthracyclines involves mainly subclinical decrease in left ventricular ejection fraction, symptomatic congestive hear failure has been observed only rarely. Based on the study PIX 301 pixantrone was approved in monotherapy in the treatment of multiple relapsed or refractory aggressive B-non-Hodgkin lymphomas. Efficacy of pixantrone combined with rituximab vs. gemcitabine + rituximab in rituximab pretreated patients is investigated in the ongoing PIX 306 study.
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Breakthrough pain

01/2017 Štěpán Rusín, Petr Jelínek
Breakthrough pain is a transitory flare of strong intensity pain in patients with otherwise well controlled and treated baseline pain. It occurs in any chronic pain, both of cancer and non-cancer type. Its treatment should be part of the treatment of any chronic pain. To solve this kind of pain, each out patient treated for chronic pain should be equipped with suitable rescue medication with rapid onset of action.
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Options sequential therapy in prostate cancer patients

01/2017 Jana Katolická
During past years, there was a significant progress in the threatment of metastatic castration-resistant prostate cancer. We have various drugs available, including those affecting androgenic receptor - enzalutamide and abiraterone, imunotherapeuthic agents - sipuleucel-T, from taxan-based chemotherapeutics we administer docetaxel and cabazitaxel and as a bone tissue targeting radiopharmaceutical, radium-223 is used. Sequentional threatment allow us to significantly prolong the survival of the patients suffering from metastatic castration-resistant prostate cancer.
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ALK inhibitors in the treatment of patients with NSCLC

01/2017 Libor Havel
Patients with EML4-ALK translocation represent small, but clinically interesting subgroup of patients with non-small cell lung cancer. Since this genetic alteration revealing we are witness of rapid progress in therapy of these patients. ALK (anaplastic lymphoma kinase) inhibitors became a standard therapy in first line treatment, second generation ALK inhibitors are available in clinical practice and higher lines are tested. This article would be a summarisation of recent attitude to ALK inhibitors in NSCLC.
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Vaccination against human papillomavirus in general practice for children and adolescents

01/2017 Alena Šebková
Preventative health care for wide population is the cornerstone of any developed country healthcare system. Preventive systems are based on local customs and practices, but, at the same time, they develop with new medical knowledge. Prevention is important not only for individuals, their wellbeing and life quality from childhood to old age, but for the society as well, from social, labor and economic perspectives. In addition to preventive checkups and screening tests, vaccination plays an important role, being an effective tool for the prevention of major infectious diseases. Typically, it's highly infectious diseases that are being vaccinated against. The rising incidence of cancer, however, requires us to provide a protection against the onset and irreversible sequelae of cancer too. Therefore, researchers are trying to find options for cancer prevention. In cancer prevention, there are currently several vaccines available, such as vaccines against Hepatitis B and Human Papilloma Virus, as both infections are associated with cancer.
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Ten years of human papillomavirus vaccination and gender issue

01/2017 Tomáš Fait
Human papillomaviruses (HPV) are the most important causes of cervical cancer but also other carcinomas and non-malignant lessions especially of women's and men's genital area. But not only. Prevention of HPV infection is the primary prevention of all HPV-associated lessions. Rules of safety sex are very important but HPV could be transfer also by noncoital activities. Ten years ago clinical history of HPV vaccination has started by quadrivalent vaccine. In 2015 it was graduated by nonavalent vaccine. All HPV vaccines are characterized by high efficacy against including types of HPV and also high safety.
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Treatment of head and neck tumors – prognostic and predictive significance of human papillomavirus

01/2017 Miloslav Pála
Squamous cell carcinomas of the head and neck are a heterogeneous group of malignancies with different pathways for pathogenesis - one mediated by tobacco and alcohol consumption and the other by human papillomavirus (HPV). These HPV-related carcinomas have distinct epidemiological and molecular characteristics and subsequent distinct biological behaviour and clinical outcome as compared with HPV-negative carcinomas. Multiple retrospective studies have shown that patients with HPV-positive oropharyngeal carcinomas are more responsive to treatment and have better prognosis. Current prospective studies are investigating whether appropriate deescalation of treatment can reduce toxicity without compromising outcomes in this group of tumours.
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Human papillomaviruses in etiopathogenesis of head and neck cancer and its epidemiology

01/2017 Jan Klozar
The incidence of human papillomaviruses (HPV) associated oropharyngeal cancer rapidly increases. HPV positive tumors are different from tobacco induced tumors biologically, epidemiologically and also by its clinical behavior. Patients with HPV positive tumors are significantly less frequently smokers and may have different sexual habits. The existence of two distinct entities of oropharyngeal cancer can in the future influence the clinical decision making, the treatment of HPV positive tumors will probably be deescalated and thus have reduced toxicity. Vaccination of the whole population together with limitation of tobacco consumption could have beneficial effect on the incidence of oropharyngeal cancer.
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The role of human papillomavirus in etiopathogenesis of anogenital cancers

01/2017 Ivan Práznovec, Petr Halada, Peter Škapinec, Jiří Špaček
Human papillomavirus is the most common cause of sexually transmitted infections. It is associated with development of anogenital tumours (cervix, vagina, vulva, anus, penis). Out of these cancers cervix has the highest incidence in the Czech Republic. Approximately 40 HPV subtypes affect anogenital area. Prooncogenic proteins E6 and E7 as well as intracellular p53 play an important role in the etiopathogenesis. HPV infection is transmissed mostly through a sexual contact.
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Laboratory aspects of human papillomavirus testing

01/2017 Kateřina Sieglová, Hana Vošmiková, Jan Laco, Ivo Šteiner
Human papillomavirus (HPV) has been known as the main etiological factor of cervical carcinoma al ready in 1983. Since then, HPV is recognized in relation with carcinomas of other organs of anogenital tract and also of the head and neck region. Recently, it became obvious that HPV-associated squamous cell carcinomas differ significantly from the HPV-negative ones - in the epidemiology, biological behavior and prognosis. Therefore, HPV testing of tumor tissue becomes clinically important. The reis a number of methods for HPV detection, with varying requirements for the biological material and also for their sensitivity, validity and cost. According to these differences, it is important to select optimal method for HPV detection.
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Human papillomaviruses and their role in the etiopathogenesis of malignant tumors

01/2017 Jan Laco
Human papillomaviruses, most commonly transmitted by sexual intercourse, are important pathogens, which significantly contribute to the formation of benign mucocutaneous lesions, e.g., squamous cell papillomas, condylomas, and warts, and of malignant tumors of anogenital and head and neck areas. They are the most important risk factors for cervical, vaginal and anal carcinomas, and they also play a role in the development of a subset of vulvar and penile carcinomas. In head and neck area, the are strongly associated with oropharyngeal carcinoma, mostly affecting palatine tonsils and root of tongue, and with a subset of sinonasal carcinomas.
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