Search results for "Schedule"
showing 10 items of 567 documents
A Phase I Study of Intravenous LBH589, a Novel Cinnamic Hydroxamic Acid Analogue Histone Deacetylase Inhibitor, in Patients with Refractory Hematolog…
2006
Abstract Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m2): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasm…
Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).
2007
Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A …
A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as …
2005
The sequential doxorubicin → CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF × 6 cycles (CMF); (b) doxorubicin × 4 cycles followed by CMF × 6 cycles (A → CMF); (c) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (CMF → GT); and (d) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (A → CMF → GT). The study used a 2 × 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A …
Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema
2005
BACKGROUND: Abdominal edema attacks in patients with hereditary angioedema are often extremely painful, associated with vomiting and diarrhea, and have a high potential for causing recurrent disability of the patient. STUDY DESIGN AND METHODS: Intraindividual comparison of retrospective data in 75 hereditary angioedema patients comprising 4,834 abdominal attacks treated with C1 inhibitor concentrate versus 17,444 untreated abdominal attacks. RESULTS: The mean duration of abdominal attacks was 92.0 hours (SD, 40.8 hr) when untreated compared to 39.9 hours (SD, 30.0 hr) when treated. Patients reported a mean maximal pain score of 8.6 (SD, 1.7; range, 1-10) for untreated attacks compared to 4.…
Work–family conflict and enrichment from the perspective of psychosocial resources: Comparing Finnish healthcare workers by working schedules
2014
Abstract We examined work–family conflict (WFC) and work–family enrichment (WFE) by comparing Finnish nurses, working dayshifts (non-shiftworkers, n = 874) and non-dayshifts. The non-dayshift employees worked either two different dayshifts (2-shiftworkers, n = 490) or three different shifts including nightshifts (3-shiftworkers, n = 270). Specifically, we investigated whether different resources, i.e. job control, managers' work–family support, co-workers' work–family support, control at home, personal coping strategies, and schedule satisfaction, predicted differently WFC and WFE in these three groups. Results showed that lower managers' work–family support predicted higher WFC only among …
Time pressure, working time control and long-term sickness absence
2015
Objectives Perceived time pressure at work has increased in most European countries during recent decades. Time pressure may be harmful for employees’ health and well-being. The aim of this register-based follow-up study is to investigate whether the effects of time pressure on long sickness absence vary by the level of working time control. Methods The data are taken from the Finnish Quality of Work Life Survey 2003 (n=3400), a representative sample of Finnish employees, combined with a register-based follow-up from Statistics Finland covering the years 2002–2006. In the 2003 survey, employees were asked about their perceived time pressure and to what extent they had control over working t…
Preliminary experience with the application of Gadolinium-DTPA before MR imaging-guided laser-induced interstitial thermotherapy of brain tumors
1997
The purpose of this study was to investigate the potential value of i.v. gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) applied before MRI-guided laser-induced interstitial thermotherapy (LITT) of brain tumors without original enhancement, especially in defining total lesion size during therapy. MRI-guided LITT was performed on two patients with astrocytoma WHO II. For both patients, Gd-DTPA was administered intravenously after a first irradiation period and LITT was continued after pulling back the light guide to coagulate the upper parts of the tumor. In both patients, the whole irreversible damaged zone of the second irradiation period after Gd-DTPA showed an intense increase …
HBV-DNA suppression and disease course in HBV cirrhosis patients on long-term lamivudine therapy
2005
In hepatitis B virus (HBV) cirrhosis patients on long-term lamivudine (LAM), the relationships between HBV suppression, development of viral resistance and disease outcome are unclear. We analysed the dynamic of serum HBV-DNA and its relationship with the clinical course of 59 patients (52 males, mean age 51.4 ±8.4 years, 12 HBeAg positive and 47 HBeAg negative, and 57 genotype D and two genotype A) with cirrhosis (45 in Child-Turcotte-Pugh class A) and high levels of serum HBV-DNA (median 14.7x107 genomes/ml) treated with LAM [median (range): 44 (15–78) months]. A total of 50 patients (84.7%) achieved a virological response (serum HBV-DNA negative by PCR) during the first 6 months of ther…
A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
2021
Aim: To determine a recommended Phase II dose of the oral fluoropyrimidine trifluridine/tipiracil (FTD/TPI) combined with the multi-kinase inhibitor regorafenib (REG) in refractory metastatic colorectal cancer patients. Materials & methods: A conventional 3 + 3 dose finding design was used. FTD/TPI was administered on days 1–5 and 8–12 of a 28-day cycle, REG on days 2–22. Two dose levels were used: FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m2 b.i.d. + REG 120 mg/d. Results: In total, 12 patients were treated at two dose levels. Three dose-limiting toxicities were observed; all were grade 3 hypertension causally attributed to REG. Recommended Phase II dose …
A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid …
2016
Abstract Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies co…