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Recurrent and/or metastatic squamous cell carcinoma of the head and neck (HNSCC) continues to be a source of significant morbidity and mortality worldwide. Agents that target the epidermal growth factor receptor (EGFR) have demonstrated beneficial effects in this setting. Cetuximab, a monoclonal antibody against the EGFR, improves locoregional control and(More)
Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 microM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG),(More)
To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five -amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1-16 mg kg(-1)), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of(More)
Treatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the last two decades as major pathways involved in pathogenesis have been elucidated. These include the vascular endothelial growth factor (VEGF) axis and mammalian target of rapamycin (mTOR). Therapies targeting the VEGF pathway include bevacizumab, sorafenib, sunitinib,(More)
The binding sites and biochemical effects of angiotensin (A) II were investigated in rat pheochromocytoma (PC12W) cells. Sarcosine1, [125I]-tyrosine4, isoleucine8-AII ([125I]-SI-AII) bound to a saturable population of sites on membranes with an equilibrium dissociation constant (Kd) of 0.4 nM and a binding site maximum of 254 fmol/mg protein. Competitive(More)
OBJECT Prophylactic cranial irradiation (PCI) is commonly offered to patients with limited stage primary small cell lung cancer following a complete response. METHODS We present the unique case of a 76-year-old woman treated with PCI with a dose of 30 Gy in 15 fractions, at 200 cGy per fraction who developed progressive dementia. CONCLUSIONS This is the(More)
PURPOSE A first-in-human clinical trial of a fully human, Fc-engineered IgG1 monoclonal antibody targeting integrin α5β1 was conducted to evaluate tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity. METHODS Escalating doses of PF-04605412 were given IV on day 1, 28 and every 2 weeks thereafter to(More)
BACKGROUND A Phase I study to determine the maximum tolerated dose (MTD) and pharmacokinetics of afatinib (BIBW 2992), a novel irreversible ErbB Family Blocker, administered orally once daily in a 3-week-on/1-week-off dosing schedule. METHODS Patients with advanced solid tumors received single-agent afatinib at 10, 20, 40, 55 or 65 mg/day. Safety,(More)
BACKGROUND This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS In all, 49 patients(More)
Angiotensin (A) II receptors on rat aortic smooth muscle (RASM) cell membranes were characterized using the radioligand [125I][Sar1Ile8]AII ([125I]SI-AII). Angiotensin I, AII, and AIII inhibited specific [125I]SI-AII binding, and their rank order of potencies, and Ki values (nM) were: AII (3.7) > AI (32.5) > or = AIII (54.0), which differed from that(More)