Petra Holečková, Libor Staněk
Ondřej Kodet, Ivana Krajsová
Libor Staněk, Robert Gurlich, Petra Tesařová, Zdeněk Musil, Luboš Petruželka
Jaromír Roubec, Radoslava Černeková
Daniel Krejčí, Jana Krejčí, Norbert Pauk
Jana Krejčí, Daniel Krejčí, Norbert Pauk
Jakub Cvek, Lukáš Knybel
Poly(ADP-ribose)polymerase inhibitors (PARP) are considered to be one of the most exciting new options for patients with ovarian carcinoma. In monotherapy, PARP inhibitors have shown the greatest activity in tumor cells carrying mutations in BRCA genes. Recent Phase III studies have shown that PARP inhibitor activity is also present in nonmutated patients, especially if they have certain clinical characteristics such as platinum sensitivity and histologically verified high-grade serous carcinoma. PARP inhibitors were also combined with chemotherapy, but overlapping myelosuppression was observed with both PARP inhibitors and chemotherapy, inhibiting the development of these combinations. In contrast, combinations of PARP inhibitors and biological agents, particularly antiangiogenic agents, appear to be well tolerated and show promising activity in both BRCA mutants and wild type BRCA. There are currently numerous clinical trials investigating the anti-tumor activity of combination therapy of PARP inhibitors.
The breast carcinoma belongs among the most frequently occurred malignant female illnesses in our country. Implementation of the screening programme enables to detect carcinoma at the I. or at the II. clinical stage in spite of the fact that the diagnosis of patients at the metastatic stage takes place, metastasis occurs by already cured patients too. Approximately 70 % of patients affected by the breast carcinoma is hormonally positive. Application of hormonal treatment has currently been prioritized for its efficiency and favourable effect with low profile of toxicity. Exception are just the patients with visceral crisis. The issue of the hormonal treatment efficiency is the creation of resistance against it. One of the ways how to postpone creation of resistance against hormonal treatment and to improve its efficiency is to combine it with the inhibitors CDK4/6.
Carcinoma of the head and neck is a one of cause of cancer-associated illness and death. Most patients present with locoregionally advanced disease, and more than 50% have recurrence within 3 years. Standard of curative care are surgery and radiotherapy. Patients with head and neck carcinoma who progressed or have metastatic disease are treated with platinum-based chemotherapy in combination event. with cetuximab. New treatments agents are checkpoint inhibitors pembrolizumab and nivolumab. Important role in diagnostics and therapy can play molecular biology and genetics.
EGFR tyrosinkinase inhibitors became a cornerstone of therapy patients with advanced non-small cell lung cancer harbouring mutations in the EGFR kinase domain. EGFR TKI therapy is characterized by high response rate and prolonged progression free survival when compared with standard platinum-based chemotherapy dublets. Despite this, vast majority of patients develope during first 12 months of therapy resistence to TKI and tumor progression. The most common mechanism of this resistence is a secondary T790M mutation. EGFR TKI of third generation are deginged to overcome this type of resistence. Osimertinib became only one of these 3rd generation tyrosinkinase inhibitors adopted for clinical use. This paper will summarize data about 3rd generation EGFR TKI in the treatment of patients with non-small cell lung cancer.
Differentiated carcinomas represent 90% of all thyroid malignancies. Median survival in radioiodine-refractory carcinomas (10-20% of all tumors) is 2.5-3.5 years. New knowledge in the field of molecular genetics has been the basis for the development of new systemic drug therapies. Sorafenib, a multikinase inhibitor, is approved for the treatment of radioiodine-refractory differentiated carcinoma on the basis of a randomized placebo-controlled clinical trial in which a longer progression of the disease was achieved in patients treated with sorafenib for 5 months. The second new drug to be registered is lenvatinib with the same indication and time to disease progression of 18.3 months. Medullar carcinoma is a rare thyroid gland tumor. The first registered drug for this diagnosis is the multikinase inhibitor of vandetanib followed by cabozantinib. In the vandetanib registration study, median time to progression was not reached and estimated age based on statistical modeling was 30.5 months. The time to progression of the disease in the clinical trial with cabozantinib was 11.2 months compared to 4.0 months for placebo.
Advances in the treatment of metastatic melanoma significantly affected the prognosis of patients with metastatic disease. Currently therapy is based on two basic therapeutic principles, namely immunotherapy with monoclonal antibodies anti-CTLA-4 and anti-PD-1 and targeted oncology therapy with BRAF inhibitors alone or in combination with MEK inhibitors. The knowledge of these therapeutic modalities leads to combination treatment, which is subject of a number of clinical trials. The work provides an overview of key contemporary knowledge and outline new options in the treatment of metastatic melanoma.
Pancreatic cancer is one of the most severe types of human tumors. It is the second most common cause of cancer deaths in the world. Worldwide, more than 300,000 new diseases are diagnosed annually and approximately the same number of patients die of this disease. In 2015, the incidence of 20/100,000 inhabitants in the Czech Republic was the second highest in the world. Despite all the advances in modern oncology treatment, the long-term survival of people with this type of malignant growth is rather exceptional. Therefore, attention is focused on the genetic causes of this cancer. Essentially, this is a genetic disease where the exact sequence of somatic DNA mutations with a multistage process is known, with the cumulative effect of mutations obtained in both coding and regulatory genes, changes in ploidy, gene amplification, structural rearrangement, deletion or loss of heterozygosity. The most frequent mutations occur in the protooncogenes of K-ras and tumor suppressor genes p16, p53, BRCA2 and DPC4/SMAD4, leading to malignant change of the epithelium of leads.
Afatinib in clinical practice – patient case study with eighteen months of progression‑free survival and high quality of life
The author presents the case report of the patient treated with afatinib. This is a man, the year 1961, in which, on June 3, 2014, a perthoraxal puncture of the left lung bearing under CT control was diagnosed with primary pulmonary adenocarcinoma of the acinaric micropapillary type according to TNM classification T4N3M1b grade IV, with bilateral metastatic lung disease, carcinomatous lymphangiitis, exudate, and metastases to the liver and thyroid. The metastasis of the thyroid gland has been verified punctually and compared to a sample of tissue taken from the lung. Performance status of ECOG 1. Molecular genetic examination on 20 June 2014 detected EGFR activation mutation in L858R exon 21, EGFR gene amplification was detected, ALK and ROS1 gene reconstruction was not found. The patient was only an occasional smoker, the patient visited his physician for weight loss of seven kilograms in three months, and dyspnoea with dry cough. Early treatment with afatinib was initiated on June 27, 2014, less than one month after tissue collection. The patient was on regular monitoring with long-term severe partial regression of lung, liver and thyroid involvement in ECOG 0 performance improvement until disease progression after 18 months of CNS treatment with a total survival of 28 months.
In the following text, we are discussing the case of a patient with non-small cell lung cancer, whom the presence of the activating mutation of the epidermal grow factor has been proved. We begun treatment with erlotinib in the first line until progression which appeared on computed tomography after 15 months. In the second line treatment she received three cycles of the chemotherapy with pemetrexed. The second line treatment was terminated due to progression and high hematotoxicity. Following the patient's wishes, further steps regarding treatment are now in the competence of the regional oncologist.
Targeted therapy is becoming more and more important part of bronchial carcinoma treatment. One of the approaches includes administering erlotinib in later lines of therapy of non-small cell carcinoma. Our two case studies document a very good therapeutical effect as well as minimal toxicity of such an approach when treating adenocarcinoma (EGFR wild-type) and/or squamous carcinoma.
The progress in radiation oncology allows stereotactic radiosurgery and radiotherapy to be used more and more frequently. Moreover, beside to dedicated stereotactic devices such as GamaKnife or CyberKnife, modern linear accelerators with a stereotactic superstructure can also be used in some indications. However, in case of spinal and lung stereotactic irradiation, the role of the CyberKnife is irreplaceable very often.
Treatment results of the gastric cancer are still unsatisfactory. Late diagnosis in European region is one of reason for these results. The disease is often diagnosed in late stage with generalisation. Adequate surgical resection is the only chance for long term survival. Type and timing of the treatment depend on decision of the multidisciplinary team. There is a summary of the diagnosis and treatment of gastric cancer in this article
Biosimilar preparations in oncology – also manufacturers of original drug associations in AIFP are developing biosimilars
Biosimilar medicinal products are not new, but monoclonal antibodies have raised the interest of the general public. At present, about 30 biosimilar products are available or are expected to be marketed prior to the very careful regulatory procedure. Oncology is one of the most economically demanding disciplines, and new biological drugs represent an extreme increase in health care costs. Increased availability of care is expected from biosimilar drugs such as rituximab, trastuzumab, bevacizumab and others.