BACKGROUND: Malignant tumours of the trachea, the lungs, and the bronchus are the second most common type of tumour in the Czech Republic. Approximately three-quarters of cases are dia-gnosed in an advanced stage (IIIB-IV) and are one of the most common causes of death in all cancer groups. Targeted therapy brings a certain level of the improvement of prognostic outlook. In the Czech Republic, 1st and 2nd generation of tyrosine kinase inhibitors (gefitinib, erlotinib, afatinib) are indicated in the first-line anticancer treatment in non-small-cell lung cancer in locally advanced and metastatic stage, with proved activating mutation status of the epidermal growth factor receptor. Erlotinib is also indicated for use in the second or third line of anticancer treatment after a documented failure of previous chemotherapy. CASE: A 70-year-old patient with lung adenocarcinoma, sensitive mutation in exon 19 of epidermal growth factor receptor gene, clinical-stage IV (according to the 7th edition of TNM classification), demonstrating long-term stable disease on erlotinib treatment after first-line gefitinib failure and second-line carboplatin-bevacizumab-paclitaxel combination chemotherapy failure. The disease treated with erlotinib has been stable for 48 months, although the dose has been reduced to 100mg per day due to side effects (rash). CONCLUSION: While the efficacy of a gefitinib treatment in this case report was comparable to clinical trials results, the progression interval in this particular patient when treated with erlotinib is about 5 times longer compared to the progression observed in clinical trials. Another interesting fact is also a significant difference in the effect of these two tyrosine kinase inhibitors, which have shown comparable efficacy in clinical trials.

• Klíčová slova
• adenocarcinoma of lung, erlotinib, gefitinib, targeted therapy, tyrosine kinase inhibitors,
• MeSH
• adenokarcinom plic farmakoterapie   genetika   MeSH
• bevacizumab terapeutické užití   MeSH
• erbB receptory genetika   MeSH
• erlotinib terapeutické užití   MeSH
• gefitinib terapeutické užití   MeSH
• karboplatina terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic farmakoterapie   genetika   MeSH
• paclitaxel terapeutické užití   MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři MeSH
• záchranná terapie metody   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• bevacizumab MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• erlotinib MeSH
• gefitinib MeSH
• karboplatina MeSH
• paclitaxel MeSH
• protinádorové látky MeSH

Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.

• Klíčová slova
• FR180204, U0126, erlotinib, infantile myofibromatosis, platelet-derived growth factor receptor, protein kinase inhibitors, receptor tyrosine kinases, sunitinib, targeted therapy,
• MeSH
• butadieny aplikace a dávkování   terapeutické užití   MeSH
• dítě MeSH
• erlotinib aplikace a dávkování   terapeutické užití   MeSH
• fosforylace účinky léků   MeSH
• inhibitory proteinkinas aplikace a dávkování   terapeutické užití   MeSH
• kojenec MeSH
• lidé MeSH
• mutace * MeSH
• myofibromatóza vrozené   farmakoterapie   genetika   MeSH
• nádorové buněčné linie MeSH
• nitrily aplikace a dávkování   terapeutické užití   MeSH
• proliferace buněk účinky léků   MeSH
• pyrazoly aplikace a dávkování   terapeutické užití   MeSH
• pyridaziny aplikace a dávkování   terapeutické užití   MeSH
• růstový faktor odvozený z trombocytů - receptor beta * genetika   metabolismus   MeSH
• sunitinib aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• butadieny MeSH
• erlotinib MeSH
• FR 180204 MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• nitrily MeSH
• PDGFRB protein, human MeSH Prohlížeč
• pyrazoly MeSH
• pyridaziny MeSH
• růstový faktor odvozený z trombocytů - receptor beta * MeSH
• sunitinib MeSH
• U 0126 MeSH Prohlížeč

BACKGROUND: Erlotinib is a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR); it is used in the treatment of advanced non-small cell lung cancer (NSCLC). We focused on the role of serum concentration of erlotinib and its association with outcome and toxicity in patients with advanced NSCLC harbouring the wild-type EGFR gene or squamous histology. PATIENTS AND METHODS: Clinical data of 122 patients were analyzed. Serum samples were collected within four weeks after the initiation of treatment. RESULTS: There was no significant association of erlotinib concentration with PFS nor OS (p=0.352 and p=0.6393). Significant associations of erlotinib concentration with grade of skin rash and diarrhoea (p<0.0001 and p<0.0001) were found. Skin rash and diarrhoea were significantly associated with PFS (p=0.0338 and p=0.0001) and OS (p=0.0064 and p=0.0353). CONCLUSION: Erlotinib concentration was not associated with outcome. Erlotinib concentration was associated with occurrence and severity of skin rash and diarrhoea; the outcome was associated with erlotinib toxicity.

• Klíčová slova
• Erlotinib, NSCLC, diarrhoea, lung cancer, serum concentration, skin rash, survival, toxicity,
• MeSH
• analýza přežití MeSH
• erbB receptory genetika   MeSH
• erlotinib škodlivé účinky   krev   terapeutické užití   MeSH
• exantém chemicky indukované   MeSH
• lidé MeSH
• nádory plic krev   farmakoterapie   genetika   MeSH
• nemalobuněčný karcinom plic krev   farmakoterapie   genetika   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky škodlivé účinky   krev   terapeutické užití   MeSH
• průjem chemicky indukované   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• erlotinib MeSH
• protinádorové látky MeSH

BACKGROUND: Squamous cell carcinoma of the lung (SCC) represents cca 30-40% of new cases of non-small cell lung cancer (NSCLC) in the Czech Republic. The tyrosine kinase inhibitor erlotinib is indicated as a 1st line treatment for patients with locally advanced and metastatic disease and activating mutations in endothelial growth factor receptor (EGFR), or as a 2nd or 3rd line treatment in EGFR-negative NSCLC patients after chemotherapeutic failure. OBSERVATION: We present three case reports of patients with SCC treated with erlotinib as a 2nd or 3rd line of treatment. All patients were verified by histological analysis of tumor samples. EGFR mutation status was negative in one patient, while the other samples were not suitable for genetic screening. RESULTS: The therapeutic response to erlotinib lasted for 68, 40, and 13 months, resp. The patient with the longest therapeutic response (patient no. 1) is still continuing erlotinib treatment (as of December 2016). The overall survival of the two patients who died was 50 and 43 months, resp. One patient died of an unknown cause with no signs of progression of the disease on CT scans. The other patient died of terminal progression of the oncological disease. All three patients experienced major therapeutic benefit from erlotinib treatment as shown by the long periods of progression-free survival and prolonged overall survival. CONCLUSION: The three case reports demonstrate that erlotinib may be effective as a 2nd or 3rd line treatment in patients with SCC, especially in patients with limited alternative anticancer treatment options.Key words: non-small cell lung cancer - squamous cell carcinoma - erlotinib - treatment - tyrosine kinase inhibitor The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 8. 2016Accepted: 14. 12. 2016.

• MeSH
• erlotinib terapeutické užití   MeSH
• lidé MeSH
• nádory plic farmakoterapie   MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři MeSH
• spinocelulární karcinom farmakoterapie   MeSH
• záchranná terapie metody   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• erlotinib MeSH
• protinádorové látky MeSH

BACKGROUND: Patients with sensitive EGFR mutations are already being treated with first and second generation tyrosine kinase inhibitors (TKIs). However, resistance to these drugs occurs over time, and over half of all cases is caused by a mutation (T790M) in the EGFR kinase domain. Osimertinib offers a new treatment option that overcomes this problem. Unfortunately, resistance to this drug also develops after several months of treatment and is caused by another mutation (C797S) in EGFR. CASE REPORT: Our case report provides evidence for the progressive development of EGFR-TKI resistance in a patient with a deletion of exon 19 in the EGFR gene. First, based on a mutation (T790M) identified after afatinib treatment and a subsequent mutation (C797S) mutation identified after osimertinib treatment. We mention overcoming this resistance (C797S) mutation by using 4th generation EGFR-TKI and other alternative procedures (chemotherapy, immunotherapy, and combinations of older EGFR-TKI generations). We also mention a rare case of peritoneal metastasis that occurred after previous treatment with osimertinib that we attempted to ameliorate by using erlotinib because the impaired condition of the patient did not allow treatment by chemotherapy. There are documented cases in which erlotinib has been successfully given to patients with peritoneal metastases and patients with the EGFR mutation C797S following progression to afatinib. This was not the case in our patient, probably because of the remaining EGFR mutation T790M. CONCLUSION: In our case report, erlotinib did not show efficacy after progression to osimetinib. Nowadays, chemotherapy is the only possible treatment in patients with good a performance status. The next-generation of TKIs are undergoing promising developments.Key words: EGFR - deletion on exon 19 - mutation T790M - mutation C797S - afatinib - osimertinibSubmitted: 12. 9. 2017Accepted: 12. 10. 2017 This project was supported by grant AZV 17-30 748A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

• MeSH
• afatinib terapeutické užití   MeSH
• akrylamidy MeSH
• aniliny MeSH
• chemorezistence genetika   MeSH
• erbB receptory genetika   MeSH
• erlotinib terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• piperaziny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• afatinib MeSH
• akrylamidy MeSH
• aniliny MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• erlotinib MeSH
• inhibitory proteinkinas MeSH
• osimertinib MeSH Prohlížeč
• piperaziny MeSH

CONTEXT: While vascular endothelial growth factor-targeted therapy and mammalian target of rapamycin inhibition are effective strategies in treating clear cell renal cell carcinoma (ccRCC), the most effective therapeutic approach for patients with non-clear cell RCC (non-ccRCC) is unknown. OBJECTIVE: To systematically review relevant literature comparing the oncological outcomes and adverse events of different systemic therapies for patients with metastatic non-ccRCC. EVIDENCE ACQUISITION: Relevant databases including MEDLINE, Embase, and the Cochrane Library were searched up to March 24, 2016. Only comparative studies were included. Risk of bias and confounding assessments were performed. A meta-analysis was planned for and only performed if methodologically appropriate; otherwise, a narrative synthesis was undertaken. EVIDENCE SYNTHESIS: The literature search identified 812 potential titles and abstracts. Five randomized controlled trials, recruiting a total of 365 patients, were included. Three studies compared sunitinib against everolimus, one of which reported the results for non-ccRCC as a subgroup rather than as an entire randomized cohort. Individually, the studies showed a trend towards favoring sunitinib in terms of overall survival and progression-free survival (PFS; Everolimus versus Sunitinib in Patients with Metastatic Non-clear Cell Renal Cell Carcinoma hazard ratio [HR]: 1.41, 80% confidence interval [CI] 1.03-1.92 and 1.41, 95% CI: 0.88-2.27, Evaluation in Metastatic Non-clear Cell Renal Cell Carcinoma HR: 1.16, 95% CI: 0.67-2.01, Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients with Metastatic Renal Cell Carcinoma HR: 1.5, 95% CI: 0.9-2.8), but this trend did not reach statistical significance in any study. Meta-analysis was performed on two studies which solely recruited patients with non-ccRCC reporting on PFS, the results of which were inconclusive (HR: 1.30, 95% CI: 0.91-1.86). Sunitinib was associated with more Grade 3-4 adverse events than everolimus, although this was not statistically significant. CONCLUSIONS: This systematic review and meta-analysis represent a robust summary of the evidence base for systemic treatment of metastatic non-ccRCC. The results show a trend towards favoring vascular endothelial growth factor-targeted therapy for PFS and overall survival compared with mammalian target of rapamycin inhibitors, although statistical significance was not reached. The relative benefits and harms of these treatments remain uncertain. Further research, either in the form of an individual patient data meta-analysis involving all relevant trials, or a randomized controlled trial with sufficient power to detect potential differences between treatments, is needed. PATIENT SUMMARY: We examined the literature to determine the most effective treatments for advanced kidney cancer patients whose tumors are not of the clear cell subtype. The results suggest that a drug called sunitinib might be more effective than everolimus, but the statistics supporting this statement are not yet entirely reliable. Further research is required to clarify this unmet medical need.

• Klíčová slova
• Chromophobe, Everolimus, Non-clear cell renal cell carcinoma, Papillary, Sunitinib, Systematic review,
• MeSH
• anilidy terapeutické užití   MeSH
• axitinib MeSH
• benzimidazoly terapeutické užití   MeSH
• bevacizumab terapeutické užití   MeSH
• chinoliny terapeutické užití   MeSH
• chinolony terapeutické užití   MeSH
• erlotinib terapeutické užití   MeSH
• everolimus terapeutické užití   MeSH
• fenylmočovinové sloučeniny terapeutické užití   MeSH
• imidazoly terapeutické užití   MeSH
• indazoly terapeutické užití   MeSH
• indoly terapeutické užití   MeSH
• interferony terapeutické užití   MeSH
• interleukin-2 terapeutické užití   MeSH
• karcinom z renálních buněk farmakoterapie   patologie   MeSH
• lidé MeSH
• nádory ledvin farmakoterapie   patologie   MeSH
• niacinamid analogy a deriváty   terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• pyrrolidinony terapeutické užití   MeSH
• pyrroly terapeutické užití   MeSH
• sirolimus analogy a deriváty   terapeutické užití   MeSH
• sorafenib MeSH
• srovnávací výzkum účinnosti MeSH
• sulfonamidy terapeutické užití   MeSH
• sunitinib MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• 4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one MeSH Prohlížeč
• anilidy MeSH
• ARQ 197 MeSH Prohlížeč
• axitinib MeSH
• benzimidazoly MeSH
• bevacizumab MeSH
• cabozantinib MeSH Prohlížeč
• chinoliny MeSH
• chinolony MeSH
• erlotinib MeSH
• everolimus MeSH
• fenylmočovinové sloučeniny MeSH
• imidazoly MeSH
• indazoly MeSH
• indoly MeSH
• interferony MeSH
• interleukin-2 MeSH
• niacinamid MeSH
• pazopanib MeSH Prohlížeč
• protinádorové látky MeSH
• pyridiny MeSH
• pyrimidiny MeSH
• pyrrolidinony MeSH
• pyrroly MeSH
• sirolimus MeSH
• sorafenib MeSH
• sulfonamidy MeSH
• sunitinib MeSH
• temsirolimus MeSH Prohlížeč
• tivozanib MeSH Prohlížeč

OBJECTIVES: To investigate the relationship of dual-phase dual-energy CT (DE-CT) and tumour size in the evaluation of the response to anti-EGFR therapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Dual-phase DE-CT was performed in 31 patients with NSCLC before the onset of anti-EGFR (erlotinib) therapy and as follow-up (mean 8 weeks). Iodine uptake (IU; mg/mL) was quantified using prototype software in arterial and venous phases; arterial enhancement fraction (AEF) was calculated. The change of IU before and after therapy onset was compared with anatomical evaluation in maximal transverse diameter and volume (responders vs. non-responders). RESULTS: A significant decrease of IU in venous phase was proved in responders according to all anatomical parameters (p=0.002-0.016). In groups of non-responders, a significant change of IU was not proved with variable trends of development. The most significant change was observed using the anatomical parameter of volume (cut-off 73 %). A significant difference of percentage change in AEF was proved between responding and non-responders (p=0.019-0.043). CONCLUSION: Dual-phase DE-CT with iodine uptake quantification is a feasible method with potential benefit in advanced assessment of anti-EGFR therapy response. We demonstrated a decrease in vascularization in the responding primary tumours and non-significant variable development of vascularization in non-responding tumours. KEY POINTS: • Dual-phase DE-CT is feasible for vascularization assessment of NSCLC with anti-EGFR therapy. • There was a significant decrease of iodine uptake in responding tumours. • There was a non-significant and variable development in non-responding tumours. • There was significant difference of AEF percentage change between responders and non-responders.

• Klíčová slova
• Dual-energy CT, Iodine contrast medium, Lung cancer, Targeted molecular therapy, Therapy response,
• MeSH
• erlotinib terapeutické užití   MeSH
• jod MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• lymfatické uzliny diagnostické zobrazování   MeSH
• nádory plic farmakoterapie   patologie   MeSH
• nemalobuněčný karcinom plic diagnóza   farmakoterapie   sekundární   MeSH
• počítačová rentgenová tomografie metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• protinádorové látky terapeutické užití   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• staging nádorů * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• erlotinib MeSH
• jod MeSH
• protinádorové látky MeSH

BACKGROUND: Serum lactate dehydrogenase (LDH) has been reported as a prognostic biomarker in malignant diseases. However, little is known on the dynamics of serum LDH levels during systemic treatment. We focused on the association of changes in serum LDH with outcome of patients with advanced-stage non-small cell lung cancer (NSCLC) treated with erlotinib. PATIENTS AND METHODS: Clinical data of 309 patients were analyzed. Serum samples were collected within one week before initiation and after one month of treatment. RESULTS: The change in serum LDH during the first month of erlotinib treatment was independently associated with disease control rate (p=0.006), progression-free survival (PFS) (p=0.010) and overall survival (OS) (p<0.001). CONCLUSION: LDH is a commonly used serum biomarker, that is cheap and easy to detect. The results of our study suggest that the change in LDH serum level during the first month is a surrogate marker on the efficacy of erlotinib in patients with advanced NSCLC.

• Klíčová slova
• EGFR-TKI, LDH, Lactate dehydrogenase, NSCLC, biomarker, erlotinib, lung cancer, prediction,
• MeSH
• dospělí MeSH
• erlotinib terapeutické užití   MeSH
• L-laktátdehydrogenasa krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic krev   farmakoterapie   MeSH
• nemalobuněčný karcinom plic krev   farmakoterapie   MeSH
• protinádorové látky terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• erlotinib MeSH
• L-laktátdehydrogenasa MeSH
• protinádorové látky MeSH

BACKGROUND: Pemetrexed and erlotinib represent different agents commonly used for the second-line treatment of patients with advanced-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We analyzed data of 137 patients with advanced-stage non-squamous NSCLC treated with pemetrexed or erlotinib in the second line. All patients harbored a wild-type epidermal growth factor receptor gene. Genetic testing was performed using a combination of denaturing capillary electrophoresis and direct Sanger sequencing. RESULTS: overall response rate and disease control rate in patients treated with pemetrexed was 20.8% and 62.5% vs. 6.3% and 53.2% in patients treated with erlotinib (p=0.022; p=0.358). Median progression-free and overall survival in patients treated with pemetrexed was 1.6 and 11.3 months vs. 1.9 and 11.4 months in patients treated with erlotinib (p=0.470 and p=0.942, respectively). Erlotinib was associated with skin rash and diarrhea; pemetrexed was associated with hematological toxicity and fatigue. CONCLUSION: A similar efficacy and different, although well-tolerated, toxicity profile of both pemetrexed and erlotinib was shown.

• Klíčová slova
• NSCLC, Pemetrexed, chemotherapy, erlotinib, second-line treatment, targeted treatment,
• MeSH
• erbB receptory genetika   MeSH
• erlotinib terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   patologie   MeSH
• pemetrexed terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• erbB receptory MeSH
• erlotinib MeSH
• pemetrexed MeSH