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ARTA treatment of metastatic castration‑resistant prostate cancer – case report
02/2021 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Vladimír Šámal, Ph.D.; MUDr. Jiří Bartoš, MBA
The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has rapidly evolved over the past 10 years. The addition chemotherapy (docetaxel, cabazitaxel), androgen receptor targeted agents (ARTA - abiraterone, enzalutamide) and radium 223 has improved outcomes for patients with mCRPC. Abiraterone in our clinical practice is applied most often before the docetaxel-based chemotherapy. We present a case study of patient with mCRPC treated by abirateron (before chemotherapy) for four years.
ENTIRE ARTICLE
The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has rapidly evolved over the past 10 years. The addition chemotherapy (docetaxel, cabazitaxel), androgen receptor targeted agents (ARTA - abiraterone, enzalutamide) and radium 223 has improved outcomes for patients with mCRPC. Abiraterone in our clinical practice is applied most often before the docetaxel-based chemotherapy. We present a case study of patient with mCRPC treated by abirateron (before chemotherapy) for four years.
Higher line treatment of metastatic renal cell carcinoma
02/2021 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Vladimír Šámal, Ph.D.; MUDr. Jiří Bartoš, MBA
Targeted therapy and immunotherapy have improved survival outcomes for patients with metastatic renal cell carcinoma. ESMO, NCCN and Czech society for oncology provide some guidelines for the most appropriate first-, secondand third-line treatment. With the growing number of available therapeutic agents and improved survival, the optimal treatment patterns in fourth-line therapy need to be examined. No robust evidence exists to optimize treatment selection in this setting. The fourth-line therapy varies significantly amongst different centers and jurisdictions.
ENTIRE ARTICLE
Targeted therapy and immunotherapy have improved survival outcomes for patients with metastatic renal cell carcinoma. ESMO, NCCN and Czech society for oncology provide some guidelines for the most appropriate first-, secondand third-line treatment. With the growing number of available therapeutic agents and improved survival, the optimal treatment patterns in fourth-line therapy need to be examined. No robust evidence exists to optimize treatment selection in this setting. The fourth-line therapy varies significantly amongst different centers and jurisdictions.
New drugs in oncology
01/2021 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Jiří Bartoš, MBA
The systemic treatment of malignant tumors has undergone significant changes in recent years. In addition to the hormonal treatment and chemotherapy, we have new therapeutic approaches as immunotherapy or targeted treatment. Many new drugs are added in the treatment of malignant tumor every year. The treatment guidelines have been updated and changed. The aim of this review is to provide summary of new drugs in treatment of solid tumors. This article presents an overview of the two groups of agents as tyrosine kinase inhibitors and monoclonal antibodies, due to extensive issues.
ENTIRE ARTICLE
The systemic treatment of malignant tumors has undergone significant changes in recent years. In addition to the hormonal treatment and chemotherapy, we have new therapeutic approaches as immunotherapy or targeted treatment. Many new drugs are added in the treatment of malignant tumor every year. The treatment guidelines have been updated and changed. The aim of this review is to provide summary of new drugs in treatment of solid tumors. This article presents an overview of the two groups of agents as tyrosine kinase inhibitors and monoclonal antibodies, due to extensive issues.
Cabozantinib treatment – case report
04/2020 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.
The Czech Republic is the world leader in the incidence of kidney cancer worldwide. Approximately 70% of renal cancers are clear cell renal, which is associated with von Hippel-Lindau (VHL) gene dysfunction. This disorder is associated with the accumulation of hypoxia-inducible factor (HIF), which results in similar metabolic events as in hypoxia. The result is the induction of vascular endothelial growth factor (VEGF) with subsequent stimulation of angiogenesis. Inhibition of angiogenesis is therefore a rational basis for therapy. According to the current reimbursement decree, sunitinib and pazopanib inhibitors are of the greatest importance in the first-line treatment of metastatic clear cell renal cell carcinoma of the vascular endothelial growth factor receptor (VEGFR). In most patients, however, the disease gradually progresses. The newer VEGFR inhibitor cabozantinib, which also acts on other signaling pathways (MET, AXL), can currently be indicated in the second line. This fact makes it possible to overcome resistance to previous VEGFR inhibitors. This is evidenced by the results of the METEOR study, where cabozantinib showed a significant prolongation of progression-free survival, overall survival and response to previous treatment with VEGFR inhibitors compared to everolimus. We started using cabozantinib in clinical practice at our workplace in 2018. Below we describe the case report of a patient treated with cabozantinib.
ENTIRE ARTICLE
The Czech Republic is the world leader in the incidence of kidney cancer worldwide. Approximately 70% of renal cancers are clear cell renal, which is associated with von Hippel-Lindau (VHL) gene dysfunction. This disorder is associated with the accumulation of hypoxia-inducible factor (HIF), which results in similar metabolic events as in hypoxia. The result is the induction of vascular endothelial growth factor (VEGF) with subsequent stimulation of angiogenesis. Inhibition of angiogenesis is therefore a rational basis for therapy. According to the current reimbursement decree, sunitinib and pazopanib inhibitors are of the greatest importance in the first-line treatment of metastatic clear cell renal cell carcinoma of the vascular endothelial growth factor receptor (VEGFR). In most patients, however, the disease gradually progresses. The newer VEGFR inhibitor cabozantinib, which also acts on other signaling pathways (MET, AXL), can currently be indicated in the second line. This fact makes it possible to overcome resistance to previous VEGFR inhibitors. This is evidenced by the results of the METEOR study, where cabozantinib showed a significant prolongation of progression-free survival, overall survival and response to previous treatment with VEGFR inhibitors compared to everolimus. We started using cabozantinib in clinical practice at our workplace in 2018. Below we describe the case report of a patient treated with cabozantinib.
Prognostic significance of primary cilia in relation to selected parameters of the tumor microenvironment of clear cell renal cell carcinoma
04/2020 MUDr. Aneta Rozsypalová; MUDr. Blanka Rosová; Mgr. Alžběta Filipová, Ph.D.; MUDr. Dimitar Hadži Nikolov, Ph.D.; Mgr. Renata Chloupková; MUDr. Igor Richter, Ph.D.; MUDr. Jan Prokš; prof. MUDr. Radoslav Matěj, Ph.D.; prof. MUDr. Roman Zachoval, Ph.D.; prof. MUDr. Bohuslav Melichar, Ph.D.; doc. MUDr. Tomáš Büchler, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.
The presence of primary cilia, programmed cell death protein-1 receptor (PD-1) expression and intraepithelial CD8+ TIL (tumor infiltrating lymphocytes) expression were retrospectively evaluated in tumor tissue blocks of the resected specimens of the kidney in 104 patients with clear cell renal cell carcinoma. Median overall survival (OS) was significantly longer in patients with lower frequency of primary cilia (<0.002) than in patients with higher frequency of primary cilia (>0.002) (p<0.001). Median OS was significantly longer in patients with lower (<25%) CD8+ TIL expression than in patients with higher (>25%) CD8+ TIL expression (p=0.006). Median OS was significantly longer in patients with lower (<25%) PD-1 expression than in patients with higher (>25%) PD-1 expression (p=0.006). The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, CD8+ TIL expression and PD-1 expression in patients with clear cell renal cell carcinoma.
ENTIRE ARTICLE
The presence of primary cilia, programmed cell death protein-1 receptor (PD-1) expression and intraepithelial CD8+ TIL (tumor infiltrating lymphocytes) expression were retrospectively evaluated in tumor tissue blocks of the resected specimens of the kidney in 104 patients with clear cell renal cell carcinoma. Median overall survival (OS) was significantly longer in patients with lower frequency of primary cilia (<0.002) than in patients with higher frequency of primary cilia (>0.002) (p<0.001). Median OS was significantly longer in patients with lower (<25%) CD8+ TIL expression than in patients with higher (>25%) CD8+ TIL expression (p=0.006). Median OS was significantly longer in patients with lower (<25%) PD-1 expression than in patients with higher (>25%) PD-1 expression (p=0.006). The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, CD8+ TIL expression and PD-1 expression in patients with clear cell renal cell carcinoma.
Bevacizumab in the treatment of uterine cervix carcinoma
03/2020 Doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Igor Richter, Ph.D.; MUDr. Jan Prokš; MUDr. Aneta Rozsypalová; MUDr. Jana Grimová
A prospective randomized phase III clinical trial, GOG 240, demonstrated a statistically significant increase in progression-free survival and overall survival in the first-line treatment of metastatic or locally advanced inoperable cervical cancer. Bevacizumab in combination with paclitaxel and cisplatin or alternatively in patients who cannot be treated with platinum, paclitaxel and topotecan, may be indicated for the treatment of adult patients with persistent, recurrent or metastatic cervical cancer.
ENTIRE ARTICLE
A prospective randomized phase III clinical trial, GOG 240, demonstrated a statistically significant increase in progression-free survival and overall survival in the first-line treatment of metastatic or locally advanced inoperable cervical cancer. Bevacizumab in combination with paclitaxel and cisplatin or alternatively in patients who cannot be treated with platinum, paclitaxel and topotecan, may be indicated for the treatment of adult patients with persistent, recurrent or metastatic cervical cancer.
Strategies sequential treatment of metastatic castration‑resistant prostate cancer
02/2020 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.; MUDr. Vladimír Šámal, Ph.D.; MUDr. Jiří Bartoš, MBA
Prostate cancer is the most common male malignant neoplasm in men worldwide and second cause of cancer related death. During the last decade, the treatment of metastatic castration resistant prostate cancer has dramatically changed with the approval of new agents as cabazitaxel, enzalutamide, abiraterone and radium 223. These new therapeutic options have provided an overall survival increase from 14-18 months to average of 30-36 months. The problem is the absence of the clearly defined predictive marker. In this review we discussing to choose the optimal treatment sequence of this disease.
ENTIRE ARTICLE
Prostate cancer is the most common male malignant neoplasm in men worldwide and second cause of cancer related death. During the last decade, the treatment of metastatic castration resistant prostate cancer has dramatically changed with the approval of new agents as cabazitaxel, enzalutamide, abiraterone and radium 223. These new therapeutic options have provided an overall survival increase from 14-18 months to average of 30-36 months. The problem is the absence of the clearly defined predictive marker. In this review we discussing to choose the optimal treatment sequence of this disease.
Immunotherapy of triple negative breast cancer
05/2019 Doc. MUDr. Josef Dvořák, PhD., MUDr. Igor Richter, Ph.D., MUDr. Jan Prokš, MUDr. Aneta Rozsypalová, MUDr. Jana Grimová
Triple negative breast cancer constitutes a heterogeneous group of diseases with limited systemic treatment options. A new perspective treatment modality is immunotherapy with check point inhibitors. The phase III randomized control trial IMpassion130 demonstrated a significantly prolonged progression free survival and overall survival in first line treatment of metastatic or locally advanced inoperable triple negative breast cancer with atezolizumab and nab-paclitaxel, exclusively in patients with programmed death-ligand 1 (PD-L1) ≥ 1 % expression on tumor infiltrating immune cells.
ENTIRE ARTICLE
Triple negative breast cancer constitutes a heterogeneous group of diseases with limited systemic treatment options. A new perspective treatment modality is immunotherapy with check point inhibitors. The phase III randomized control trial IMpassion130 demonstrated a significantly prolonged progression free survival and overall survival in first line treatment of metastatic or locally advanced inoperable triple negative breast cancer with atezolizumab and nab-paclitaxel, exclusively in patients with programmed death-ligand 1 (PD-L1) ≥ 1 % expression on tumor infiltrating immune cells.
Influence of neoadjuvant chemoradiotherapy on PD‑L1 expression change in rectal cancer patients
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.
ENTIRE ARTICLE
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.
First‑line treatment of metastatic renal cell carcinoma
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.
ENTIRE ARTICLE
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.
The position of bevacizumab in the treatment of colorectal cancer
06/2018 MUDr. Igor Richter, Ph.D., doc. MUDr. Josef Dvořák, Ph.D., MUDr. Jiří Bartoš, MBA
Metastatic colorectal cancer is one of the day-to-day diagnoses of oncology centers. In addition to chemotherapy, we also have the opportunity to receive targeted treatment. Bevacizumab is a monoclonal antibody against vascular endothelial factor and we have more than ten years of experience with it. The review article evaluates the current status of bevacizumab in the treatment of metastatic colorectal cancer, where its position in the treatment algorithm of the disease has recently been clarified without a clear predictive factor. Finally, there is a case report of the patient who responds well to chemotherapy in combination with bevacizumab in the first line, despite left-hand localization and the non-mutated RAS gene.
ENTIRE ARTICLE
Metastatic colorectal cancer is one of the day-to-day diagnoses of oncology centers. In addition to chemotherapy, we also have the opportunity to receive targeted treatment. Bevacizumab is a monoclonal antibody against vascular endothelial factor and we have more than ten years of experience with it. The review article evaluates the current status of bevacizumab in the treatment of metastatic colorectal cancer, where its position in the treatment algorithm of the disease has recently been clarified without a clear predictive factor. Finally, there is a case report of the patient who responds well to chemotherapy in combination with bevacizumab in the first line, despite left-hand localization and the non-mutated RAS gene.
Cabazitaxel in the treatment of metastatic prostate cancer
03/2018 MUDr. Igor Richter, Ph.D.; doc. MUDr. Josef Dvořák, Ph.D.
Prostate cancer is the most common male malignant neoplasm in men worldwide and second cause of cancer related death. In castrate-resistance prostate cancer (CRPC) we can see the development of the new therapeutic options. The chemotherapy is an important part of the CRPC treatment. Cabazitaxel, a new generation taxane, demonstrates the overall survival prolongation as first substances in patients with metastatic CRPC after previous treatment by docetaxel. The discussed issues are to find the optimal treatment sequences. The aim of this presented article is to define the status of cabazitaxel in CRPC.
ENTIRE ARTICLE
Prostate cancer is the most common male malignant neoplasm in men worldwide and second cause of cancer related death. In castrate-resistance prostate cancer (CRPC) we can see the development of the new therapeutic options. The chemotherapy is an important part of the CRPC treatment. Cabazitaxel, a new generation taxane, demonstrates the overall survival prolongation as first substances in patients with metastatic CRPC after previous treatment by docetaxel. The discussed issues are to find the optimal treatment sequences. The aim of this presented article is to define the status of cabazitaxel in CRPC.
Current treatment options for metastatic castration‐resistant prostate cancer
02/2018 MUDr. Aneta Rozsypalová, doc. MUDr. Josef Dvořák, Ph.D., MUDr. Igor Richter, Ph.D., MUDr. David Buka, MUDr. Jana Grimová, MUDr. Michaela Matoušková
Prostate cancer is mostly hormonal dependent disease from the beginning but during sometime develops in castration-resistant prostate cancer - it is time when the progression of the disease is occurring despite androgen deprivation therapy and patients have a testosterone level drawn. Many trials are interested in finding new opportunities of treatment of this stage. Thanks these trials we have new drugs: in category of cytotoxic chemotherapy cabazitaxel, new generation of androgen deprivation therapy ARTA (abirateron acetate, enzalutamide). For patients with bone-only metastatic disease, without visceral metastasis, there is an opportunity to use radium 223. And we can't forget immunotherapy agents as sipuleucel-T and check point inhibitors. So we have many opportunities which significantly prolong median of overall survival with good quality of life.
ENTIRE ARTICLE
Prostate cancer is mostly hormonal dependent disease from the beginning but during sometime develops in castration-resistant prostate cancer - it is time when the progression of the disease is occurring despite androgen deprivation therapy and patients have a testosterone level drawn. Many trials are interested in finding new opportunities of treatment of this stage. Thanks these trials we have new drugs: in category of cytotoxic chemotherapy cabazitaxel, new generation of androgen deprivation therapy ARTA (abirateron acetate, enzalutamide). For patients with bone-only metastatic disease, without visceral metastasis, there is an opportunity to use radium 223. And we can't forget immunotherapy agents as sipuleucel-T and check point inhibitors. So we have many opportunities which significantly prolong median of overall survival with good quality of life.
Enzalutamide in treatment in patients with metastatic castration‑resistant prostate cancer after previous chemotherapy
03/2017 MUDr. Igor Richter, Ph.D., doc. MUDr. Josef Dvořák, Ph.D., MUDr. Věra Hejzlarová, MUDr. Jiří Bartoš, MBA
Introduction: The aim of this retrospective study is demonstrated efficacy and tolerance of enzalutamide therapy in real clinical practice in 33 patients with metastatic castration-resistant prostate cancer (mCRPC) who had previous chemotherapy.
Patients and methods: Between November 2014 and June 2016 we treated with enzalutamide a total of 33 patients with metastatic castrate resistant prostate cancer. The all patients were previous treated by one or two lines of chemotherapy. The enzalutamide was administered by standard dose 160 mg daily.
Results: One patient had cerebral hemorrhage grade IV. In other patients the non-hematological toxicity evaluation did not achieve the grade III or IV. Anemia grade III-IV was described in 6 patients and thrombocytopenia grade III-IV in 2 patients. The median of progression free survival was 7.0 (95% CI 6.1-7.9) months. The median of overal survival was 8.4 (95 % CI 5.1-11.7) months.
Conclusion: The study demonstrated our first experience with enzalutamid in postchemo-indication in patients with mCRPC with good toleration and efficacy.
ENTIRE ARTICLE
Introduction: The aim of this retrospective study is demonstrated efficacy and tolerance of enzalutamide therapy in real clinical practice in 33 patients with metastatic castration-resistant prostate cancer (mCRPC) who had previous chemotherapy.
Patients and methods: Between November 2014 and June 2016 we treated with enzalutamide a total of 33 patients with metastatic castrate resistant prostate cancer. The all patients were previous treated by one or two lines of chemotherapy. The enzalutamide was administered by standard dose 160 mg daily.
Results: One patient had cerebral hemorrhage grade IV. In other patients the non-hematological toxicity evaluation did not achieve the grade III or IV. Anemia grade III-IV was described in 6 patients and thrombocytopenia grade III-IV in 2 patients. The median of progression free survival was 7.0 (95% CI 6.1-7.9) months. The median of overal survival was 8.4 (95 % CI 5.1-11.7) months.
Conclusion: The study demonstrated our first experience with enzalutamid in postchemo-indication in patients with mCRPC with good toleration and efficacy.