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5 results on '"Carbazoles/therapeutic use"'

1. Effects of Carvedilol on Plasma Levels of Pro-Inflammatory Cytokines.

Author

Kurum, Turhan, Tatli, Ersan, and Yuksel, Mahmut

Subjects
*CYTOKINES, *ISCHEMIA, *BLOOD plasma, *BIOMARKERS, *CARDIOMYOPATHIES, *INTERLEUKIN-6, *TUMOR necrosis factors
Abstract

We prospectively investigated the effects of adding carvedilol to the standard treatment of ischemic and nonischemic dilated cardiomyopathy (DCM), by measuring the plasma levels of pro-inflammatory cytokines. Sixty patients with DCM (35 ischemic and 25 nonischemic) were divided into 2 subgroups: patients on standard therapy alone (digoxin, angiotensin-converting enzyme inhibitors, and diuretics) and patients on standard therapy plus carvedilol. Study participants' serum levels of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) were measured at the beginning and again at the end of the study. Left ventricular ejection fraction and left ventricular diastolic function were evaluated by means of radionuclide ventriculography. In ischemic patients on carvedilol, levels of IL-6 and TNF-α dropped significantly (P= 0.028 and P=0.034, respectively). In ischemic patients on standard treatment, plasma IL-2 levels were elevated after treatment (P=0.047). No significant differences occurred in IL-6 levels, while TNF-α levels were elevated (P=0.008). In nonischemic patients on carvedilol, IL-6 and TNF-α levels dropped significantly (P=0.018 and P=0.004, respectively). The left ventricular ejection fraction increased significantly (P=0.006). In nonischemic patients on standard treatment, no significant change occurred in any value. Carvedilol suppressed the plasma levels of TNF-α and IL-6 in both ischemic and nonischemic patients. The carvedilol effect was more pronounced in patients with nonischemic dilated cardiomyopathy than in those with ischemic disease. [ABSTRACT FROM AUTHOR] more...

Published
2007

2. Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer

Author

Rafael Rosell, Alice T. Shaw, Ali Zeaiter, Shirish M. Gadgeel, Emmanuel Mitry, Bogdana Balas, Jin S. Ahn, Maurice Perol, Johannes Noe, Sai-Hong Ignatius Ou, Peter N. Morcos, D. Ross Camidge, Solange Peters, Tony Mok, Dong Wan Kim, Rafal Dziadziuszko, Sophie Golding, ALEX Trial Investigators, Nordman, I., Pittman, K., Dear, R., Lwin, Z., Briggs, P., Pavlakis, N., Ceric, T., Mehic, B., Stanetic, M., Franke, F.A., Castro, G., Santo Borges, G., Pereira, J., Brust, L., Santos, L., Cruz, M., Ribeiro, R., De Azevedo, S., Neron, Y.V., Sangha, R., Cohen, V., Burkes, R., Abdelsalam, M., Yadav, S., Cheema, P., Yanez, E., Aren, O., Zhou, C., Zhang, L., Liu, X., Corrales Rodriguez, L., Meldgaard, P., Soerensen, J.B., McCulloch, T., Rodriguez, N., Gaafar, R., Abdel Azeem, H., Coudert, B., Moro-Sibilot, D., Lena, H., Bennouna, J., Cortot, A., Veillon, R., Cadranel, J., Barlesi, F., Reck, M., Mezger, J., von Pawel, J., Fischer, J.R., Dickgreber, N.K., Zarogoulidis, K., Syrigos, K., Georgoulias, V., Agelaki, S., Castro-Salguero, H., Ho, J., Chan, S.H., Cheng, C.K., Ng, A., Stemmer, S., Wollner, M., Gottfried, M., Dudnik, J., Cyjon, A., Heching, N., Novello, S., Tiseo, M., Platania, M., Misino, A., Gridelli, C., Ciardiello, F., Favaretto, A., De Marinis, F., Longo, F., Bordonaro, R., Dazzi, C., Chiari, R., Mercuri, E., Macedo, E., Rodriguez Cid, J.R., McKeage, M., Vera, L., Morón Escobar, H.D., Rodriguez, M., Mas, L., Ramlau, R., Kowalski, D., Szczesna, A., Kazarnowicz, A., Milanowski, J., Luboch-Kowal, J., Oliveira, J., Barata, F., Almodovar, T., Lee, J.S., Cho, B.C., Kim, S.W., Han, J.Y., Karaseva, N., Stroyakovskii, D., Kuzmin, A., Smolin, A., Laktionov, K., Ragulin, Y., Filippov, A., Levchenko, E., Jovanovic, D., Perin, B., Andric, Z., Soo, R., Tan, E.H., De Castro Carpeno, J., Provencio Pulla, M., Garrido Lopez, P., Felip Font, E., Morano Bueno, T., Sanchez, A., Isla Casado, D., Ponce Aix, S., Reguart Aransay, N., Viteri Ramirez, S., Rodriguez Abreu, D., Sanchez Torres, J.M., Massuti Sureda, B., Ramos Vazquez, M., Tabernero, J.M., Curioni, A., Rothschild, S., Scherz, A., Chiu, C.H., Su, W.C., Yang, CHJ, Chang, G.C., Hsia, T.C., Yang, C.T., Tharavichitkul, E., Pongthai, P., Arpornwirat, W., Geater, S., Srimuninnimit, V., Sriuranpong, V., Demirkazik, A., Goker, E., Harputluoglu, H., Cicin, I., Kose, F., Erman, M., Bondarenko, I., Vinnyk, Y., Shparyk, Y., Golovko, Y., Lal, R., Forster, M., Califano, R., Skailes, G., Thompson, J., Mekhail, T., Polikoff, J., Spigel, D., Waqar, S., Hermann, R., Deo, E., Simon, G., Rybkin, I., Kaywin, P.R., Uyeki, J., Gubens, M., Limaye, S., Gerber, D.E., Leal, T., Spira, A.I., Bazhenova, L., Cetnar, J., Socinski, M., Jahanzeb, M., Kabbinavar, F., Lawler, W.E., Hancock, M.R., Raez, L.E., DiCarlo, B.A., Lowe, T.E., Fidler, M., Ross, H., Davidson, S.J., Sanchez, J.D., Hamm, J., Kerr, S., Belman, N., Baker, S., Naraev, B., Jung, G., Edelman, M., Feldman, L., Belani, C., and Pakkala, S. more...

Subjects
Adult, Male, 0301 basic medicine, Oncology, Alectinib, medicine.medical_specialty, Pathology, Lung Neoplasms, Brigatinib, Pyridines, medicine.drug_class, Carbazoles, Antineoplastic Agents, Kaplan-Meier Estimate, Aged, 80 and over, Animals, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, Carbazoles/adverse effects, Carbazoles/therapeutic use, Carcinoma, Non-Small-Cell Lung/drug therapy, Carcinoma, Non-Small-Cell Lung/mortality, Central Nervous System Neoplasms/drug therapy, Central Nervous System Neoplasms/secondary, Disease-Free Survival, Female, Follow-Up Studies, Humans, Intention to Treat Analysis, Lung Neoplasms/drug therapy, Lung Neoplasms/mortality, Middle Aged, Piperidines/adverse effects, Piperidines/therapeutic use, Protein Kinase Inhibitors/adverse effects, Protein Kinase Inhibitors/therapeutic use, Pyrazoles/adverse effects, Pyrazoles/therapeutic use, Pyridines/adverse effects, Pyridines/therapeutic use, Receptor Protein-Tyrosine Kinases/analysis, Receptor Protein-Tyrosine Kinases/antagonists & inhibitors, Young Adult, Central Nervous System Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Piperidines, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, Internal medicine, medicine, Anaplastic lymphoma kinase, Lung cancer, Protein Kinase Inhibitors, Crizotinib, Ceritinib, business.industry, Receptor Protein-Tyrosine Kinases, General Medicine, medicine.disease, Lorlatinib, ALK inhibitor, 030104 developmental biology, 030220 oncology & carcinogenesis, Pyrazoles, business, medicine.drug
Abstract

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P more...

Published
2017
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3. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study

Author

Alice T. Shaw, Shirish M. Gadgeel, Solange Peters, S-H.I. Ou, Silvia Novello, Ali Zeaiter, Maurice Pérol, Anna Wrona, D.R. Camidge, Dong Wan Kim, Bogdana Balas, Eveline Nüesch, Ting Liu, Tony Mok, and Rafael Rosell more...

Subjects
0301 basic medicine, Alectinib, Oncology, Male, Adult, Aged, Aged, 80 and over, Anaplastic Lymphoma Kinase/antagonists & inhibitors, Anaplastic Lymphoma Kinase/genetics, Brain/diagnostic imaging, Brain/drug effects, Brain/radiation effects, Brain Neoplasms/diagnostic imaging, Brain Neoplasms/genetics, Brain Neoplasms/secondary, Brain Neoplasms/therapy, Carbazoles/pharmacology, Carbazoles/therapeutic use, Carcinoma, Non-Small-Cell Lung/diagnostic imaging, Carcinoma, Non-Small-Cell Lung/genetics, Carcinoma, Non-Small-Cell Lung/secondary, Carcinoma, Non-Small-Cell Lung/therapy, Chemoradiotherapy/methods, Crizotinib/pharmacology, Crizotinib/therapeutic use, Disease Progression, Female, Humans, Lung/diagnostic imaging, Lung/drug effects, Lung/radiation effects, Lung Neoplasms/diagnostic imaging, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Lung Neoplasms/therapy, Magnetic Resonance Imaging, Middle Aged, Piperidines/pharmacology, Piperidines/therapeutic use, Treatment Outcome, Tumor Burden/drug effects, Tumor Burden/radiation effects, Young Adult, Lung Neoplasms, ALK+, medicine.medical_treatment, 0302 clinical medicine, Piperidines, Carcinoma, Non-Small-Cell Lung, Clinical endpoint, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, Lung, Brain Neoplasms, Hazard ratio, Brain, Hematology, Chemoradiotherapy, Tumor Burden, 030220 oncology & carcinogenesis, CNS, medicine.drug, medicine.medical_specialty, Carbazoles, 03 medical and health sciences, Crizotinib, Internal medicine, medicine, Carcinoma, Lung cancer, non-small-cell lung cancer, business.industry, medicine.disease, Radiation therapy, 030104 developmental biology, business
Abstract

The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX. Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression. In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib, n = 64; crizotinib, n = 58), 43 had measurable lesions (alectinib, n = 21; crizotinib, n = 22), and 46 had received prior radiotherapy (alectinib, n = 25; crizotinib, n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25-0.64] and those without (HR 0.51, 95% CI: 0.33-0.80, P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not. Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advanced ALK+ NSCLC, irrespective of prior CNS disease or radiotherapy. ClinicalTrials.gov NCT02075840. more...

Published
2018

5. Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy

Author

Ole Gøtzsche, Jens Refsgaard, Morten Bøttcher, Frederik Andreasen, and Torsten Toftegaard Nielsen

Subjects
Blood Glucose, Male, Vasodilator Agents, Glucose uptake, Myocardial Ischemia, Cardiomyopathy, Myocardial Ischemia/complications, Carbazoles/therapeutic use, Propanolamines, Catecholamines, Prospective Studies, Carvedilol, Ejection fraction, Dipyridamole, Middle Aged, Coronary Vessels, Heart Failure/diagnostic imaging, Propanolamines/therapeutic use, Treatment Outcome, Echocardiography, Cardiology, Dipyridamole/administration & dosage, Vasodilator Agents/therapeutic use, Female, Cardiology and Cardiovascular Medicine, Perfusion, medicine.drug, Tomography, Emission-Computed, medicine.medical_specialty, Carbazoles, Catecholamines/blood, Statistics, Nonparametric, Blood Glucose/drug effects, Double-Blind Method, Internal medicine, medicine, Humans, Aged, Heart Failure, Analysis of Variance, Ischemic cardiomyopathy, business.industry, Coronary Vessels/drug effects, Microcirculation, medicine.disease, Microcirculation/drug effects, Heart failure, business
Abstract

In a randomized (2:1), double-blinded design study, we studied 25 patients with congestive heart failure (66 +/- 9 years, ejection fraction 30 +/- 7%) before and after 23-week treatment with the beta blocker carvedilol 25 mg twice daily (n = 17) or placebo (n = 8) in addition to standard therapy. Using dynamic positron emission tomography, myocardial perfusion at rest and perfusion reserve after dipyridamole (0.56 mg/kg/min) were measured. Myocardial glucose uptake and plasma levels of catecholamines were also estimated. Carvedilol treatment reduced the rate-pressure product (8,781 +/- 2,672 vs 6,342 +/- 1,346, p more...

Published
2002
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