BACKGROUND: In a prospective study with long-term follow-up, we analyzed circulating T cell subsets in patients with metastatic colorectal cancer (mCRC) in the context of primary tumor sidedness, KRAS status, and clinical outcome. Our primary goal was to investigate whether baseline levels of circulating T cell subsets serve as a potential biomarker of clinical outcome of mCRC patients treated with an anti-VEGF-based regimen. METHODS: The study group consisted of 36 patients with colorectal adenocarcinoma who started first-line chemotherapy with bevacizumab for metastatic disease. We quantified T cell subsets including Tregs and CD8+ T cells in the peripheral blood prior to therapy initiation. Clinical outcome was evaluated as progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: 1) mCRC patients with KRAS wt tumors had higher proportions of circulating CD8+ cytotoxic T cells among all T cells but also higher measures of T regulatory (Treg) cells such as absolute count and a higher proportion of Tregs in the CD4+ subset. 2) A low proportion of circulating Tregs among CD4+ cells, and a high CD8:Treg ratio at initiation of VEGF-targeting therapy, were associated with favorable clinical outcome. 3) In a subset of patients with primarily right-sided mCRC, superior PFS and OS were observed when the CD8:Treg ratio was high. CONCLUSIONS: The baseline level of circulating immune cells predicts clinical outcome of 1st-line treatment with the anti-VEGF angio/immunomodulatory agent bevacizumab. Circulating immune biomarkers, namely the CD8:Treg ratio, identified patients in the right-sided mCRC subgroup with favorable outcome following treatment with 1st-line anti-VEGF treatment.

• Klíčová slova
• Anti-VEGF, Antitumor immune response, Metastatic colorectal cancer, Primary colorectal carcinoma sidedness, Regulatory T cells, T cell subsets,
• MeSH
• adenokarcinom krev   farmakoterapie   mortalita   patologie   MeSH
• bevacizumab aplikace a dávkování   terapeutické užití   MeSH
• cytotoxické T-lymfocyty metabolismus   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• inhibitory angiogeneze aplikace a dávkování   terapeutické užití   MeSH
• kolorektální nádory krev   farmakoterapie   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů farmakoterapie   MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• následné studie MeSH
• počet lymfocytů MeSH
• prospektivní studie MeSH
• protoonkogenní proteiny p21(ras) analýza   MeSH
• regulační T-lymfocyty metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   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
• bevacizumab MeSH
• inhibitory angiogeneze MeSH
• KRAS protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny p21(ras) MeSH
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč

PURPOSE: The goal of our analysis was to study pretherapeutic circulating 25-OHD plasma levels in patients with previously untreated advanced gastric cancer treated in the randomised controlled phase III Erbitux (cetuximab) in combination with Xeloda (capecitabine) and cisplatin in advanced esophago-gastric cancer (EXPAND) trial (NCT00678535) and to explore whether low 25-OHD plasma levels are associated with worse prognosis and may compromise the clinical efficacy of cetuximab. METHODS: Six hundred thirty patients with available pretherapeutic 25-OHD plasma levels and treated with chemotherapy based on capecitabine and cisplatin, or chemotherapy and cetuximab, were included. The Cox proportional hazard regression model was used to analyse the association between low 25-OHD and survival in both treatment arms. RESULTS: Majority of study patients were found to have severe vitamin D deficiency. No prognostic impact of 25-OHD plasma levels could be found in our patient cohort, and there was no indication of an interference of 25-OHD plasma levels and the efficacy of treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. CONCLUSIONS: Although majority of patients with advanced gastric cancer show hypovitaminosis D deficiency, there is no proof for a negative impact on survival or reduced treatment response. A prospective study is needed to investigate the potential benefit of vitamin D supplementation in this patient cohort during first-line chemotherapy.

• Klíčová slova
• 25-OHD plasma levels, Chemotherapy cetuximab, Gastric cancer, Prognosis, Vitamin D,
• MeSH
• adenokarcinom krev   farmakoterapie   mortalita   MeSH
• capecitabinum terapeutické užití   MeSH
• cetuximab terapeutické užití   MeSH
• cisplatina terapeutické užití   MeSH
• erbB receptory antagonisté a inhibitory   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory žaludku krev   farmakoterapie   mortalita   MeSH
• nedostatek vitaminu D epidemiologie   MeSH
• prevalence MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• vitamin D krev   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
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• capecitabinum MeSH
• cetuximab MeSH
• cisplatina MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• humanizované monoklonální protilátky MeSH
• vitamin D MeSH

Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.

• Klíčová slova
• Pancreatic ductal adenocarcinoma, diagnosis, miR-21-5p, microRNAs, plasma, prognosis,
• MeSH
• adenokarcinom krev   patologie   chirurgie   MeSH
• duktální karcinom slinivky břišní krev   patologie   chirurgie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA krev   MeSH
• míra přežití MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory slinivky břišní krev   patologie   chirurgie   MeSH
• následné studie MeSH
• předoperační péče * MeSH
• prognóza MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA MeSH
• MIRN21 microRNA, human MeSH Prohlížeč
• nádorové biomarkery MeSH

INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide; therefore, understanding the biological or clinical role of tumor-associated antigens and autoantibodies is of eminent interest for designing antitumor immunotherapeutic strategies. METHODS: Here we prospectively analyzed the serum frequencies of New York esophageal squamous cell carcinoma 1 (NY-ESO-1), human epidermal growth factor 2/neu, and melanoma-associated antigen A4 (MAGE-A4) antibodies and expression of the corresponding antigens in tumors of 121 patients with NSCLC undergoing an operation without prior neoadjuvant chemotherapy and compared them with those in 57 control age-matched patients with no history of a malignant disease. RESULTS: We found that only antibodies specific for NY-ESO-1 (19.8% [n = 24 of 121]) were significantly increased in the group of patients with NSCLC compared with in the controls. NY-ESO-1 seropositivity was significantly positively associated with an active smoking history in patients with NSCLC but not in smokers from the control group. In tumors, the frequency of NY-ESO-1 mRNA expression was 6.3% (in four of 64 patients), the frequency of human epidermal growth factor 2/neu (HER 2/neu) expression was 11.9% (five of 42), and the frequency of MAGE-A4 expression was 35.1% (20 of 57). MAGE-A4 expression in tumors correlated with smoking status and male sex in patients with NSCLC. Patients with squamous cell carcinoma displayed higher expression of NY-ESO-1 and MAGE-A4 in tumors than did patients with adenocarcinoma. On the other hand, 94.7% of nonsmoking patients in our study had adenocarcinoma (of whom 73.7% were women). CONCLUSION: These results confirm the reported high immunogenicity of NY-ESO-1 and suggest that a smoking-induced chronic inflammatory state might potentiate the development of NY-ESO-1-specific immune responses. Moreover, smoking might contribute to the expression of other cancer/testis antigens such as MAGE-A4 at early stages of NSCLC development.

• Klíčová slova
• MAGE-A4 autoantibodies, NSCLC, NY-ESO-1, Smoking, Tumor antigens,
• MeSH
• adenokarcinom krev   etiologie   patologie   MeSH
• antigeny nádorové krev   imunologie   MeSH
• dospělí MeSH
• kouření škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny krev   imunologie   MeSH
• nádorové biomarkery krev   MeSH
• nádorové proteiny krev   MeSH
• nádory plic krev   etiologie   patologie   MeSH
• následné studie MeSH
• nemalobuněčný karcinom plic krev   etiologie   patologie   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• receptor erbB-2 krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom krev   etiologie   patologie   MeSH
• staging nádorů MeSH
• studie případů a kontrol 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
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antigeny nádorové MeSH
• CTAG1B protein, human MeSH Prohlížeč
• ERBB2 protein, human MeSH Prohlížeč
• MAGEA4 protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH
• receptor erbB-2 MeSH

BACKGROUND AND OBJECTIVES: Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. METHODS: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. RESULTS: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. CONCLUSIONS: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

• Klíčová slova
• PSA, Vaccinium macrocarpon, adenocarcinoma, cancer markers, randomized controlled trial, urinary metabolites.,
• MeSH
• adenokarcinom krev   dietoterapie   moč   MeSH
• down regulace MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory prostaty krevní zásobení   dietoterapie   moč   MeSH
• oxidační stres fyziologie   MeSH
• potravní doplňky MeSH
• předoperační péče MeSH
• prostatektomie metody   MeSH
• prostatický specifický antigen metabolismus   MeSH
• senioři MeSH
• Vaccinium macrocarpon * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• nádorové biomarkery MeSH
• prostatický specifický antigen MeSH

BACKGROUND: Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. METHODS: A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had ⩾1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. RESULTS: None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI=0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI=0.38, 1.22) and low (HR=0.73, 95% CI=0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. CONCLUSIONS: REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.

• MeSH
• adenokarcinom krev   chemie   farmakoterapie   MeSH
• dospělí MeSH
• gastroezofageální junkce MeSH
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• jednoduchá slepá metoda MeSH
• Kaplanův-Meierův odhad MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• multicentrické studie jako téma MeSH
• nádorové biomarkery MeSH
• nádorové proteiny analýza   antagonisté a inhibitory   krev   MeSH
• nádory žaludku krev   chemie   farmakoterapie   mortalita   MeSH
• přežití bez známek nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• ramucirumab MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor analýza   antagonisté a inhibitory   MeSH
• receptor erbB-2 analýza   MeSH
• receptory vaskulárního endoteliálního růstového faktoru krev   MeSH
• retrospektivní studie MeSH
• vaskulární endoteliální růstové faktory krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ERBB2 protein, human MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• inhibitory angiogeneze MeSH
• KDR protein, human MeSH Prohlížeč
• monoklonální protilátky MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH
• protinádorové látky MeSH
• receptor 2 pro vaskulární endoteliální růstový faktor MeSH
• receptor erbB-2 MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• vaskulární endoteliální růstové faktory MeSH

BACKGROUND: Visfatin is an adipocytokine produced primarily by visceral adipose tissue. In addition to its effect on the insulin receptor, it is a proinflammmatory cytokine with accumulating evidence for its rise in circulation, accompanying systemic inflammation. The aim of this study was to evaluate changes in serum visfatin levels in the early post-abdominal surgery period with serum levels of other proinflammatory cytokines, to determine whether it could be used as a marker of inflammation. METHODS AND RESULTS: This was a prospective cross-sectional study of 42 patients undergoing elective laparotomic right hemicolectomy for adenocarcinoma colon. The parameters determined were visfatin, leptin, adiponectin, TNF α, interleukin-6 and C-reactive protein levels. The dynamics of change in these markers were assessed at +12, +24, +48, and +72 h after surgery. Serum levels of visfatin peaked as early as 24 h post-surgery, returning to normal after 72 h. TNF α and IL-6 levels reached their maximum 12 to 24 h later while CRP levels peaked after 72 h. CONCLUSIONS: Significantly increased serum levels of visfatin detected in the early period after abdominal surgery preceded increase in the levels of other proinflammatory markers including TNF α, IL-6, and CRP. Given its dynamics, visfatin could serve as an early predictor of the development of inflammatory changes in patients undergoing surgery, particularly those with obesity (BMI > 30 kg/m(2)).

• Klíčová slova
• abdominal surgery, proinflammatory cytokines, visceral obesity, visfatin,
• MeSH
• adenokarcinom krev   chirurgie   MeSH
• kolektomie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory tračníku krev   chirurgie   MeSH
• následné studie MeSH
• nikotinamidfosforibosyltransferasa krev   MeSH
• pooperační komplikace krev   epidemiologie   MeSH
• pooperační období MeSH
• prevalence MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• nádorové biomarkery MeSH
• nikotinamidfosforibosyltransferasa MeSH

BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

• Klíčová slova
• IGF-1 receptor, biomarker, ganitumab, gemcitabine, pancreatic cancer,
• MeSH
• adenokarcinom krev   farmakoterapie   mortalita   sekundární   MeSH
• časové faktory MeSH
• deoxycytidin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• gemcitabin MeSH
• humanizované monoklonální protilátky MeSH
• intravenózní podání MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nádorové biomarkery krev   MeSH
• nádory slinivky břišní krev   farmakoterapie   mortalita   patologie   MeSH
• přežití bez známek nemoci MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• protinádorové antimetabolity aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• rozvrh dávkování léků 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
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• deoxycytidin MeSH
• ganitumab MeSH Prohlížeč
• gemcitabin MeSH
• humanizované monoklonální protilátky MeSH
• monoklonální protilátky MeSH
• nádorové biomarkery MeSH
• protinádorové antimetabolity MeSH

BACKGROUND: Tumor biomarkers are used for predicting therapy effect and prognosis of patients with non-small cell lung cancer (NSCLC). We focused on their potential role in prediction of the efficacy of erlotinib. PATIENTS AND METHODS: In a total of 144 patients with advanced-stage (IIIB or IV) NSCLC treated with erlotinib, pre-treatment levels of soluble carcinoembryonic antigen (CEA) and cytokeratin markers in serum were measured. RESULTS: The median progression-free and overall survival for patients with a high level of carcinoembryonic antigen (CEA) was 1.9 and 8.6 vs. 2.9 and 16.1 months for patients with low CEA (p=0.046 and p=0.116). The respective medians for patients with a high level of cytokeratin-19 fragment were 1.9 and 6.1 vs. 3.4 and 23.8 months for patients with the low cytokeratin-19 fragment (p<0.001 and p<0.001). CONCLUSION: High pre-treatment serum levels of one or both biomarkers are associated with poor outcome of patients with NSCLC treated with erlotinib.

• Klíčová slova
• CEA, CYFRA 21-1, EGFR-TKI, NSCLC, Tumor marker, erlotinib, prediction,
• MeSH
• adenokarcinom krev   farmakoterapie   mortalita   MeSH
• antigeny nádorové krev   MeSH
• chinazoliny terapeutické užití   MeSH
• dospělí MeSH
• erbB receptory antagonisté a inhibitory   genetika   MeSH
• erlotinib MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• karcinoembryonální antigen krev   MeSH
• keratin-19 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mutace genetika   MeSH
• nádorové biomarkery krev   MeSH
• nádory plic krev   farmakoterapie   mortalita   MeSH
• následné studie MeSH
• nemalobuněčný karcinom plic krev   farmakoterapie   mortalita   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom krev   farmakoterapie   mortalita   MeSH
• staging nádorů 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
• práce podpořená grantem MeSH
• Názvy látek
• antigen CYFRA21.1 MeSH Prohlížeč
• antigeny nádorové MeSH
• chinazoliny MeSH
• EGFR protein, human MeSH Prohlížeč
• erbB receptory MeSH
• erlotinib MeSH
• inhibitory proteinkinas MeSH
• karcinoembryonální antigen MeSH
• keratin-19 MeSH
• nádorové biomarkery MeSH

BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. INTERPRETATION: Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.

• MeSH
• adenokarcinom krev   farmakoterapie   MeSH
• antagonisté androgenů terapeutické užití   MeSH
• benzamidy MeSH
• fenylthiohydantoin analogy a deriváty   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty krev   farmakoterapie   MeSH
• nitrily MeSH
• prostatický specifický antigen krev   MeSH
• protinádorové látky terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• antagonisté androgenů MeSH
• benzamidy MeSH
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• nitrily MeSH
• prostatický specifický antigen MeSH
• protinádorové látky MeSH