Search results for "time factor"
showing 10 items of 3219 documents
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial.
2012
BACKGROUND & AIMS: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were randomized to receive either sorafenib 400mg or matching placebo orally b.i.d. on a continuous basis. Because HCC is a heterogeneous disease, baseline patient characteristics may affect individual responses to treatment. In a comprehensive series of exploratory subgroup analyses, data from the SHARP trial were analyzed to discern if baseline patient characteristics influenced the efficacy and safety o…
Behavioural sensitization to repeated sleep deprivation in a mice model of mania.
2008
Sensitization to the effect of stress has been hypothesized as a mechanism to explain episode recurrence and cycle acceleration in bipolar disorder. Naturalistic observations and experimental work in human patients suggested that sleep deprivation can trigger manic episodes of illness. In rats sleep deprivation (SD) with the platform method caused mania-like behaviours thus providing an animal model of mania with face, construct, and predictive validity. In the present study we administered SD or control stress to male CD1 mice following a dose-response protocol based on time of exposure to the experimental conditions (6, 12 or 24 h) and repetition of treatment (three times). SD, but not st…
Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.
2015
Background Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting. Methods Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents. Results Cancer stem cells were extracted from liver metas…
Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to thre…
2007
BACKGROUND: This randomised phase III study investigated if in responsive and stable disease (SD) stage IV patients after two courses of cisplatin and gemcitabine, single-agent gemcitabine (experimental arm) was not inferior in terms of overall survival (OS) to cisplatin-gemcitabine (standard arm). PATIENTS AND METHODS: Noninferiority was defined as an increase in the hazard of death (HR) < or = 1.33 in the experimental arm. From January 2001 to February 2004, 340 patients were registered and 250 were randomised. Cisplatin was administered on day 1 at 75 mg/m2 and Gemcitabine on days 1 and 8 at 1250 mg/m2 every 3 weeks. RESULTS: Response rate after two courses was 29%. The 1-year progressio…
Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of r…
2015
BackgroundAcquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance.MethodsWe compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing.ResultsAmong 132 samples, putative resistance mechanisms were identified in 58%, including NRAS o…
Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study
2018
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks tra…
Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (Neo…
2011
Summary Background Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting. Methods In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg…
Sorafenib: from literature to clinical practice
2013
Sorafenib is considered the standard systemic therapy for hepatocellular carcinoma (HCC), in patients with well-preserved liver function (Child-Pugh A class) and advanced-stage HCC (BCLC-C) or in patients with HCC progressing after locoregional therapies, with a high grade of recommendation. The approval of sorafenib for this indication was grounded on the efficacy and the safety results reported by two international randomized, controlled trials, the SHARP and the Asia-Pacific studies. In addition, the efficacy and the safety of sorafenib in clinical practice are addressed by several field-practice experiences, including the multinational GIDEON study and the SOFIA study. Finally, further …
Staging systems of hepatocellular carcinoma: A review of literature
2013
Hepatocellular carcinoma (HCC) is a major health problem with a high incidence and mortality all over the world. Natural history of HCC is severe and extremely variable, and prognostic factors influencing outcomes are incompletely defined. Over time, many staging and scoring systems have been proposed for the classification and prognosis of patients with HCC. Currently, the non-ideal predictive performance of existing prognostic systems is secondary to their inherent limitations, as well as to a non-universal reproducibility and transportability of the results in different populations. New serological and histological markers are still under evaluation with promising results, but they requi…
Post-transplant consolidation based on combination of lenalidomide and proteasome inhibitors in multiple myeloma
2021
Multiple myeloma (MM) is a hematological malignancy due to uncontrolled proliferation of neoplastic plasma cells in the bone marrow, associated to chromosomal instability and cytogenetic abnormalities, which could have an impact on prognosis. Response to treatment and survival of newly diagnosed myeloma patients is heterogeneous, with median overall survival ranging from two to more than ten years, due to clinical and biological factors. To warrant long-term control of disease, several strategies have been proposed in the last years, including short-term high-dose of treatment, named as consolidation, before maintenance. This review will discuss the role of consolidation in the current myel…