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- Escudier, Bernard, et al.
(författare)
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Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
- 2009
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 27:25, s. 4068-4075
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen. PATIENTS AND METHODS: Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures. RESULTS: One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM. CONCLUSION: Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.
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| 2. |
- Krum, Henry, et al.
(författare)
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Effect on Mode of Death of Heart Failure Treatment Started with Bisoprolol Followed by Enalapril, Compared to the Opposite Order: Results of the Randomized CIBIS III Trial
- 2011
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Ingår i: Cardiovascular Therapeutics. - : Wiley. - 1755-5914. ; 29:2, s. 89-98
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Tidskriftsartikel (refereegranskat)abstract
- P>Background: Mode of death in chronic heart failure (CHF) may be of relevance to choice of therapy for this condition. Sudden death is particularly common in patients with early and/or mild/moderate CHF. beta-Blockade may provide better protection against sudden death than ACE inhibition (ACEI) in this setting. Methods: We randomized 1010 patients with mild or moderate, stable CHF and left ventricular ejection fraction < 35%, without ACEI, beta-blocker or angiotensin-receptor-blocker therapy, to either bisoprolol (n = 505) or enalapril (n = 505) for 6 months, followed by their combination for 6-24 months. The two strategies were blindly compared regarding adjudicated mode of death, including sudden death and progressive pump failure death. Results: During the monotherapy phase, 8 of 23 deaths in the bisoprolol-first group were sudden, compared to 16 of 32 in the enalapril-first group: hazard ratio (HR) for sudden death 0.50; 95% confidence interval (CI) 0.21-1.16; P = 0.107. At 1 year, 16 of 42 versus 29 of 60 deaths were sudden: HR 0.54; 95% CI 0.29-1.00; P = 0.049. At study end, 29 of 65 versus 34 of 73 deaths were sudden: HR 0.84; 95% CI 0.51-1.38; P = 0.487. Comparable figures for pump failure death were: monotherapy, 7 of 23 deaths versus 2 of 32: HR 3.43; 95% CI 0.71-16.53; P = 0.124, at 1 year, 13 of 42 versus 5 of 60: HR 2.57; 95% CI 0.92-7.20; P = 0.073, at study end, 17 of 65 versus 7 of 73: HR 2.39; 95% CI 0.99-5.75; P = 0.053. There were no significant between-group differences in any other fatal events. Conclusion: Initiating therapy with bisoprolol compared to enalapril decreased the risk of sudden death during the first year in this mild systolic CHF cohort. This was somewhat offset by an increase in pump failure deaths in the bisoprolol-first cohort.
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| 3. |
- Porth, Oliver, et al.
(författare)
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The Event Horizon General Relativistic Magnetohydrodynamic Code Comparison Project
- 2019
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 243:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in compact object astrophysics, especially the discovery of merging neutron stars by LIGO, the imaging of the black hole in M87 by the Event Horizon Telescope, and high- precision astrometry of the Galactic Center at close to the event horizon scale by the GRAVITY experiment motivate the development of numerical source models that solve the equations of general relativistic magnetohydrodynamics (GRMHD). Here we compare GRMHD solutions for the evolution of a magnetized accretion flow where turbulence is promoted by the magnetorotational instability from a set of nine GRMHD codes: Athena++, BHAC, Cosmos++, ECHO, H-AMR, iharm3D, HARM-Noble, IllinoisGRMHD, and KORAL. Agreement among the codes improves as resolution increases, as measured by a consistently applied, specially developed set of code performance metrics. We conclude that the community of GRMHD codes is mature, capable, and consistent on these test problems.
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| 4. |
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| 5. |
- Willenheimer, Ronnie, et al.
(författare)
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Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure With Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence. Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III.
- 2005
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Ingår i: Circulation. - 1524-4539. ; 112:16, s. 2426-2435
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Tidskriftsartikel (refereegranskat)abstract
- Background - In patients with chronic heart failure (CHF), a beta-blocker is generally added to a regimen containing an angiotensin-converting-enzyme ( ACE) inhibitor. It is unknown whether beta-blockade as initial therapy may be as useful. Methods and Results - We randomized 1010 patients with mild to moderate CHF and left ventricular ejection fraction <= 35%, who were not receiving ACE inhibitor, beta-blocker, or angiotensin receptor blocker therapy, to open-label monotherapy with either bisoprolol ( target dose 10 mg QD; n = 505) or enalapril ( target dose 10 mg BID; n = 505) for 6 months, followed by their combination for 6 to 24 months. The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually. Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the ;95% confidence interval (CI) for the absolute between-group difference was < 5%, corresponding to a hazard ratio (HR) of 1.17. In the intention-to-treat sample, the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment ( absolute difference - 1.6%, 95% CI - 7.6 to 4.4%, HR 0.94; 95% CI 0.77 to 1.16). In the per-protocol sample, 163 patients allocated to bisoprolol-first treatment had a primary end point, versus 165 allocated to enalapril-first treatment ( absolute difference - 0.7%, 95% CI - 6.6 to 5.1%, HR 0.97; 95% CI 0.78 to 1.21). With bisoprolol-first treatment, 65 patients died, versus 73 with enalapril-first treatment ( HR 0.88; 95% CI 0.63 to 1.22), and 151 versus 157 patients were hospitalized ( HR 0.95; 95% CI 0.76 to 1.19). Conclusion - Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril.
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| 6. |
- Witjes, J. Alfred, et al.
(författare)
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EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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