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The future of drug development in oncology lies in identifying subsets of patients who will benefit from particular therapies, using predictive biomarkers. These technologies offer hope of enhancing the value of cancer medicines and reducing the size, cost and failure rates of clinical trials. However, examples of the failure of predictive biomarkers also(More)
PURPOSE Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the(More)
PURPOSE A fully human monoclonal antibody to anti-alpha(v) integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. EXPERIMENTAL DESIGN In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was(More)
PURPOSE HER3 is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This first-in-human study of U3-1287 (NCT00730470), a fully human anti-HER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics in patients with advanced solid tumor. EXPERIMENTAL DESIGN The study was(More)
Integrins are heterodimeric cell adhesion receptors that mediate intercellular communication through cell-extracellular matrix interactions and cell-cell interactions. Integrins have been demonstrated to play a direct role in cancer progression, specifically in tumor cell survival, tumor angiogenesis, and metastasis. Therefore, agents targeted against(More)
Purpose: The purpose of this randomized, two-period crossover study was to determine the pharmacokinetics of orally administered topotecan in the presence and absence of oral ranitidine. Methods: Patients with solid malignant tumors refractory to standard treatment were given topotecan orally on a daily times five schedule repeated every 21 days. Topotecan(More)
Whereas over 85% of human cancers are solid tumors, of the 8 monoclonal antibodies (mAbs) currently approved for cancer therapy, 25% are directed at solid tumor surface antigens (Ags). This shortfall may be due to barriers to achieving adequate exposure in solid tumors. Advancements in tumor biology, protein engineering, and theoretical modeling of(More)
Carcinogenesis involves the acquisition of multiple genetic changes altering various cellular phenotypes. These changes occur within the fixed time period of a human lifespan, and mechanisms that accelerate this process are more likely to result in clinical cancers. Mutator mutations decrease genome stability and, hence, accelerate the accumulation of(More)
PURPOSE Aberrant Notch signaling has been implicated in the pathogenesis of many human cancers. MK-0752 is a potent, oral inhibitor of γ-secretase, an enzyme required for Notch pathway activation. Safety, maximum-tolerated dose, pharmacokinetics (PKs), pharmacodynamics, and preliminary antitumor efficacy were assessed in a phase I study of MK-0752. (More)
A multicentre, randomised study was carried out in Europe, South Africa and North America to compare the activity and tolerability of oral versus intravenous (i.v.) topotecan in patients with relapsed epithelial ovarian cancer. Patients who had failed first-line therapy after one platinum-based regimen, which could have included a taxane, were randomised to(More)