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BACKGROUND We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. METHODS From November 2003 to March 2005, we randomly assigned 903 patients with renal-cell carcinoma that was resistant to(More)
Since the molecular revolution of the 1980s, knowledge of the aetiology of cancer has increased considerably, which has led to the discovery and development of targeted therapies tailored to inhibit cancer-specific pathways. The introduction and refinement of rapid, high-throughput screening technologies over the past decade has greatly facilitated this(More)
PURPOSE This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period.(More)
BACKGROUND Response remains an important endpoint in clinical cancer trials. However, the prognostic utility of best tumor response in metastatic renal cell carcinoma (mRCC) remains vague. OBJECTIVE To define the prognostic relevance of the depth of remission in mRCC. DESIGN, SETTING, AND PARTICIPANTS Pooled data from the Pfizer database for 2749(More)
PURPOSE OSI-906 is a potent inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR). The purpose of this study was to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906 in patients with advanced solid tumors. PATIENTS AND METHODS This was a nonrandomized, open-label, phase I,(More)
PURPOSE The renin-angiotensin system may play a role in carcinogenesis. The purpose of this study was to evaluate the impact of angiotensin system inhibitors (ASI) on outcomes in metastatic renal cell carcinoma (mRCC) patients treated in the targeted therapy era. EXPERIMENTAL DESIGN We conducted a pooled analysis of mRCC patients treated on phase II and(More)
The expression of excitatory amino acid transporters (EAATs) in rat hippocampus was studied following kainic acid-induced seizure activity in vivo and in hippocampal slice cultures. Protein and mRNA levels of the glial (EAAT2) and neuronal (EAAT3) transporters were determined with affinity-purified antibodies and oligonucleotide probes, respectively.(More)
BACKGROUND Bone metastases (BMs) are frequently present in patients with metastatic renal cell carcinoma (mRCC) and cause significant morbidity. OBJECTIVE The purpose of this analysis was to assess the impact of BMs and bisphosphonate therapy (BT) on outcomes in mRCC. DESIGN, SETTING, AND PARTICIPANTS We conducted a pooled analysis of patients with mRCC(More)
Angiogenesis is critical for the growth and proliferation of tumors as well as for normal development. We now describe a novel role for histidine-rich glycoprotein (HRGP) in the modulation of angiogenesis. HRGP is a plasma protein that circulates in relatively high concentrations (1.5 microM), but has no known function in vivo. We have shown previously that(More)
7002 Background: Sorafenib, an oral multi-kinase inhibitor, targets the Raf/MEK/ERK pathway at the level of Raf kinase and receptor tyrosine kinases, and has shown efficacy against several tumor types in phase I/II trials. Non-small-cell lung cancer (NSCLC) is associated with mutations in k-ras, upstream of Raf/MEK/ERK. METHODS This multi-center,(More)