Selected articles
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Current status of durvalumab in the lung cancer treatment
05/2021 Doc. MUDr. David Vrána, Ph.D.
Lung cancer represents one of the most frequent type of cancer. They can be classified as non-small cell lung cancer and small cell lung cancer. The treatment strategy of these tumors unfortunately didn't change significantly over the last couple years until the immunotherapy and tyrosine kinase inhibitors were launched into daily clinical practice. Immunotherapy, more specifically checkpoint inhibitors has quickly established their role in the treatment of several tumor types and nowadays has confirmed their effectivity in the first line of the palliative treatment of the non-small cell and small cell lung cancer including the maintenance therapy of the non-small cell lung cancer after radical chemoradiotherapy. Durvalumab is the monoclonal antibody against programmed cell death-ligand 1 (PD-L1), which blocks the interaction of the ligand PD-L1 and programmed cell death 1 receptor (PD-1) / CD80 which leads the significant increase in the immune response against cancer. At the same time this influencing of the immunity has brought the new adverse events which are different from the adverse events of the chemotherapy or tyrosine kinase inhibitors.
ENTIRE ARTICLE
Lung cancer represents one of the most frequent type of cancer. They can be classified as non-small cell lung cancer and small cell lung cancer. The treatment strategy of these tumors unfortunately didn't change significantly over the last couple years until the immunotherapy and tyrosine kinase inhibitors were launched into daily clinical practice. Immunotherapy, more specifically checkpoint inhibitors has quickly established their role in the treatment of several tumor types and nowadays has confirmed their effectivity in the first line of the palliative treatment of the non-small cell and small cell lung cancer including the maintenance therapy of the non-small cell lung cancer after radical chemoradiotherapy. Durvalumab is the monoclonal antibody against programmed cell death-ligand 1 (PD-L1), which blocks the interaction of the ligand PD-L1 and programmed cell death 1 receptor (PD-1) / CD80 which leads the significant increase in the immune response against cancer. At the same time this influencing of the immunity has brought the new adverse events which are different from the adverse events of the chemotherapy or tyrosine kinase inhibitors.
Systemic treatment strategy for metastatic colorectal cancer in 2020, emphasis on new molecules
02/2021 Doc. MUDr. David Vrána, Ph.D.
The treatment of the metastatic colorectal cancer is unfortunately mostly palliative. There are new molecules which have entered the treatment algorithm of the colorectal cancer. From the immunotherapy pembrolizumab, nivolumab or combination of nivolumab with ipilimumab have been approved by the Food and Drug Administration (FDA) for the previously treated colorectal cancer with mismatch repair deficiency / high microsatellite instability (dMMR/MSI-H) and also pembrolizumab has gained approval FDA in the first line palliative treatment. In the Czech Republic unfortunately there are all these molecules in the diagnosis of colorectal cancer without registration and without reimbursement. At the same time there is new combination of cetuximab with encorafenib in previously treated patients with BRAF V600E mutation unfortunately without reimbursement.
ENTIRE ARTICLE
The treatment of the metastatic colorectal cancer is unfortunately mostly palliative. There are new molecules which have entered the treatment algorithm of the colorectal cancer. From the immunotherapy pembrolizumab, nivolumab or combination of nivolumab with ipilimumab have been approved by the Food and Drug Administration (FDA) for the previously treated colorectal cancer with mismatch repair deficiency / high microsatellite instability (dMMR/MSI-H) and also pembrolizumab has gained approval FDA in the first line palliative treatment. In the Czech Republic unfortunately there are all these molecules in the diagnosis of colorectal cancer without registration and without reimbursement. At the same time there is new combination of cetuximab with encorafenib in previously treated patients with BRAF V600E mutation unfortunately without reimbursement.
Cemiplimab in the treatment of non‑melanoma skin tumors
01/2021 Doc. MUDr. David Vrána, Ph.D.
Non-melanoma skin cancer represents the most frequent cancer overall. Radiotherapy and surgery are the main treatment modalities; however, the best choice depends on tumor location, patient age, comorbidities and also patienťs preference. A small portion of these patients unfortunately progress into locally advanced or metastatic form when surgery and radiotherapy are not possible. Cemiplimab represents another check-point inhibitor molecule (belongs among programmed cell death protein 1 receptor inhibitors [PD-1]) which has proven effectivity and safety in clinical trials for the treatment of locally advancedor metastatic squamous cell and basal cell carcinoma where surgery and radiotherapy are not feasible. Cemiplimab is another reasonable treatment choice for this group of patients since effectivity of conventional chemotherapy is limited.
ENTIRE ARTICLE
Non-melanoma skin cancer represents the most frequent cancer overall. Radiotherapy and surgery are the main treatment modalities; however, the best choice depends on tumor location, patient age, comorbidities and also patienťs preference. A small portion of these patients unfortunately progress into locally advanced or metastatic form when surgery and radiotherapy are not possible. Cemiplimab represents another check-point inhibitor molecule (belongs among programmed cell death protein 1 receptor inhibitors [PD-1]) which has proven effectivity and safety in clinical trials for the treatment of locally advancedor metastatic squamous cell and basal cell carcinoma where surgery and radiotherapy are not feasible. Cemiplimab is another reasonable treatment choice for this group of patients since effectivity of conventional chemotherapy is limited.
Combination of nivolumab and ipilimumab in the first‑line treatment of non‑small cell lung cancer
01/2021 Doc. MUDr. David Vrána, Ph.D.
Metastatic non-small cell lung cancer represents a disease with poor prognosis. Introducing tyrosine kinase inhibitors of specific mutations into daily practice improved the prognosis of a group of patients, however for majority of the patients before the era of immunotherapy the chemotherapy was the only option. Several molecules working as immunotherapeutic agents have proven their effectivity and safety in the first and second line of palliative treatment of the lung cancer. Recently the combination of nivolumab with ipilimumab was introduced into the clinical practice based on the CheckMate 227 and CheckMate 9LA trials. Combined immunotherapy with nivolumab and ipilimumab represents a new treatment option for patients with non-small cell lung cancer without specific mutations regardless of programmed cell death-ligand 1 (PD-L1) expression. Registration in the Czech Republic as well as health care reimbursement is unfortunately missing at this moment for this new combination.
ENTIRE ARTICLE
Metastatic non-small cell lung cancer represents a disease with poor prognosis. Introducing tyrosine kinase inhibitors of specific mutations into daily practice improved the prognosis of a group of patients, however for majority of the patients before the era of immunotherapy the chemotherapy was the only option. Several molecules working as immunotherapeutic agents have proven their effectivity and safety in the first and second line of palliative treatment of the lung cancer. Recently the combination of nivolumab with ipilimumab was introduced into the clinical practice based on the CheckMate 227 and CheckMate 9LA trials. Combined immunotherapy with nivolumab and ipilimumab represents a new treatment option for patients with non-small cell lung cancer without specific mutations regardless of programmed cell death-ligand 1 (PD-L1) expression. Registration in the Czech Republic as well as health care reimbursement is unfortunately missing at this moment for this new combination.
News in systemic treatment of metastatic gastric cancer and gastroesophageal junction cancer
03/2020 Doc. MUDr. David Vrána, Ph.D.
The goals of the treatment of the gastric and gastroesophageal junction adenocarcinoma is the quality of life, symptoms palliation and improvement in the overall survival. The generally recommended regimen in the first line setting is the chemotherapy combination based on platinum derivates (cisplatin or oxaliplatin) eventually with trastuzumab in tumors with HER2 overexpression. Nowadays, pembrolizumab is also the treatment of choice in the first line. The standard regimen in the second and later lines is much less defined. For patients in good performance status paclitaxel with ramucirumab remains generally recommended treatment of choice eventually monotherapy with taxane, irinotecan or capecitabine. In patients with MSI-H (microsatellite instability-high) or dMMR (deficient mismatch repair) tumors pembrolizumab is the treatment of choice. In third line of the treatment trifluridine/tipiracil is the new treatment standard. The aim of this article is to summarize the current treatment strategy of the locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma.
ENTIRE ARTICLE
The goals of the treatment of the gastric and gastroesophageal junction adenocarcinoma is the quality of life, symptoms palliation and improvement in the overall survival. The generally recommended regimen in the first line setting is the chemotherapy combination based on platinum derivates (cisplatin or oxaliplatin) eventually with trastuzumab in tumors with HER2 overexpression. Nowadays, pembrolizumab is also the treatment of choice in the first line. The standard regimen in the second and later lines is much less defined. For patients in good performance status paclitaxel with ramucirumab remains generally recommended treatment of choice eventually monotherapy with taxane, irinotecan or capecitabine. In patients with MSI-H (microsatellite instability-high) or dMMR (deficient mismatch repair) tumors pembrolizumab is the treatment of choice. In third line of the treatment trifluridine/tipiracil is the new treatment standard. The aim of this article is to summarize the current treatment strategy of the locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma.
Atezolizumab in the treatment of non-small cell lung cancer
01/2020 MUDr. Gyula Nyárs; doc. MUDr. David Vrána, Ph.D.
Atezolizumab is a modified humanized IgG1 monoclonal antibody that inhibits programmed death-ligand 1 (PD-L1). It is the one of few check-point inhibitors which can be used to treat patients with non-small cell lung cancer. Although it is currently registered in the Czech Republic only for the second and higher lines of palliative treatment after progression on chemotherapy or targeted therapy, unfortunately health insurance still does not reimburse it. The goal of this article is to summarize outcomes of the most important studies which proved the efficacy and safety of atezolizumab in the first and second line of palliative treatment.
ENTIRE ARTICLE
Atezolizumab is a modified humanized IgG1 monoclonal antibody that inhibits programmed death-ligand 1 (PD-L1). It is the one of few check-point inhibitors which can be used to treat patients with non-small cell lung cancer. Although it is currently registered in the Czech Republic only for the second and higher lines of palliative treatment after progression on chemotherapy or targeted therapy, unfortunately health insurance still does not reimburse it. The goal of this article is to summarize outcomes of the most important studies which proved the efficacy and safety of atezolizumab in the first and second line of palliative treatment.
HITHOC – possibility of combined treatment of malignant pleural mesothelioma
05/2019 Doc. MUDr. David Vrána, Ph.D.; MUDr. Nikol Rušarová; MUDr. Marek Szkorupa, Ph.D.
Malignant pleural mesothelioma represents a disease with poor prognosis. There is currently no accepted general standard of care however as available published data indicate the multimodality approach combining chemotherapy (neoadjuvant or adjuvant, based on cisplatin/carboplatin and pemetrexed), surgery and eventually perioperative pleural chemotherapy lavage seem to bring the most benefit. This approach is suitable for only limited group of patients in a good performance status, without any distant metastatic disease and without clinically significant comorbidities. Further research is therefore needed to define the optimal treatment algorithm for malignant pleural mesothelioma.
ENTIRE ARTICLE
Malignant pleural mesothelioma represents a disease with poor prognosis. There is currently no accepted general standard of care however as available published data indicate the multimodality approach combining chemotherapy (neoadjuvant or adjuvant, based on cisplatin/carboplatin and pemetrexed), surgery and eventually perioperative pleural chemotherapy lavage seem to bring the most benefit. This approach is suitable for only limited group of patients in a good performance status, without any distant metastatic disease and without clinically significant comorbidities. Further research is therefore needed to define the optimal treatment algorithm for malignant pleural mesothelioma.
Current treatment management of metastatic HER-2+/HER-2- breast cancer
02/2019 MUDr. Nikol Rušarová, MUDr. Marie Bartoušková, doc. MUDr. David Vrána, Ph.D.
Breast cancer is the most frequently diagnosed cancer and despite the gains in early detection, up to 5 percent of women are diagnosed with metastatic disease at the time of first presentation. Due to development of new molecules breast cancer is now a chronic disease, while metastatic disease is still incurable. It is a heterogeneous diverse disease composed of several biologic subtypes that have distinct behaviors and responses to therapy.
ENTIRE ARTICLE
Breast cancer is the most frequently diagnosed cancer and despite the gains in early detection, up to 5 percent of women are diagnosed with metastatic disease at the time of first presentation. Due to development of new molecules breast cancer is now a chronic disease, while metastatic disease is still incurable. It is a heterogeneous diverse disease composed of several biologic subtypes that have distinct behaviors and responses to therapy.
Biosimilar trastuzumab – are we afraid or looking forward?
04/2018 Doc. MUDr. David Vrána, Ph.D.
Trastuzumab represents one of the fundamental targeted molecule in oncological practice. Due to the high breast cancer incidence, constantly increasing patient survival with HER2 positive breast cancer the overall treatment cost is increasing rapidly. Since the patent of Herceptin has expired there is an intense effort to replace the Herceptin with cheaper equivalents. Biosimilars represents one of the possible option. Recently there are several trastuzumab biosimilars registered by EMA (Ontruzant, Kanjinti, Herzuma) and further molecules are in the approval process. The usage of the biosimilars may represent the saving about 20-30% of the original price and this could possible extend the insurance reimbursement to further indications. Biosimilars are used in Czech Republic for many years with generally good experience however due to the different approval proces of the biosimilars compared with original drugs there has to be a caution about possible side effects which may not manifest during the testing on relatively small group of patients.
ENTIRE ARTICLE
Trastuzumab represents one of the fundamental targeted molecule in oncological practice. Due to the high breast cancer incidence, constantly increasing patient survival with HER2 positive breast cancer the overall treatment cost is increasing rapidly. Since the patent of Herceptin has expired there is an intense effort to replace the Herceptin with cheaper equivalents. Biosimilars represents one of the possible option. Recently there are several trastuzumab biosimilars registered by EMA (Ontruzant, Kanjinti, Herzuma) and further molecules are in the approval process. The usage of the biosimilars may represent the saving about 20-30% of the original price and this could possible extend the insurance reimbursement to further indications. Biosimilars are used in Czech Republic for many years with generally good experience however due to the different approval proces of the biosimilars compared with original drugs there has to be a caution about possible side effects which may not manifest during the testing on relatively small group of patients.
The side location of colorectal cancer affects the prognosis and treatment strategy
02/2018 Doc. MUDr. David Vrána, Ph.D.
Colorectal cancer represents second most frequent cancer in the population. In the last years there is a growing evidence about predictive and prognostic role of the tumor location in the gut in the case of metastatic cancer. There are several possible explanations based on the embryogenesis of the gut, bacterial colonization or genetic predisposition. Retrospective evaluation of clinical trials with targeted therapy (panitumumab, cetuximab) has clearly proven the advantage of anti-EGFR treatment in the case of left-sided colorectal cancer however not in right-sided cancer. Right-sided colorectal cancer has worse prognosis regardless of treatment. This difference is also apparent in subsequent treatment lines. In summary, side location represents predictive factor for anti-EGFR therapy and probably only predictive factor for bevacizumab treatment.
ENTIRE ARTICLE
Colorectal cancer represents second most frequent cancer in the population. In the last years there is a growing evidence about predictive and prognostic role of the tumor location in the gut in the case of metastatic cancer. There are several possible explanations based on the embryogenesis of the gut, bacterial colonization or genetic predisposition. Retrospective evaluation of clinical trials with targeted therapy (panitumumab, cetuximab) has clearly proven the advantage of anti-EGFR treatment in the case of left-sided colorectal cancer however not in right-sided cancer. Right-sided colorectal cancer has worse prognosis regardless of treatment. This difference is also apparent in subsequent treatment lines. In summary, side location represents predictive factor for anti-EGFR therapy and probably only predictive factor for bevacizumab treatment.