Robert A. Beckman

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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)
Malignancies are characterized by mutations. We have hypothesized that the thousands of mutations in most human cancers do not result from the low mutation rates exhibited by normal human cells. Instead, cancer cells express a mutator phenotype (i.e., the mutation rate in the cancer cells is much greater than that in normal cells). We consider the following(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)
The idea, originating in the early years of the 20th century, that each cancer is an independent somatic evolutionary process has been abundantly confirmed by modern molecular approaches (1–3). Genetic and epigenetic changes that increase the chance of outgrowth of the developing tumor are successively selected for. It has, however, often been argued that(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)
Epidemiologic data and molecular biology have combined to demonstrate that multiple genetic changes may be required in carcinogenesis. Mutator mutations, defined as genetic changes which increase the rate of genetic change, including both single base changes and chromosomal instability, may accelerate this process. Key questions remain in defining the role(More)
PURPOSE Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. (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)
BACKGROUND Efatutazone (CS-7017), a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone. METHODS Patients with advanced solid malignancies and no(More)