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BACKGROUND Alterations in hedgehog signaling are implicated in the pathogenesis of basal-cell carcinoma. Although most basal-cell carcinomas are treated surgically, no effective therapy exists for locally advanced or metastatic basal-cell carcinoma. A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway,(More)
PURPOSE We evaluated the efficacy and safety of bevacizumab in patients with platinum-resistant epithelial ovarian carcinoma (EOC) or peritoneal serous carcinoma (PSC) who had experienced disease progression during, or within 3 months of discontinuing, topotecan or liposomal doxorubicin. PATIENTS AND METHODS No more than three prior treatment regimens(More)
PURPOSE Vismodegib, a Hedgehog pathway inhibitor, has preclinical activity in colorectal cancer (CRC) models. This trial assessed the efficacy, safety, and pharmacokinetics of adding vismodegib to first-line treatment for metastatic CRC (mCRC). EXPERIMENTAL DESIGN Patients were randomized to receive vismodegib (150 mg/day orally) or placebo, in(More)
With the increasing availability of newly discovered biomarkers personalized drug development is becoming more commonplace. Unless evidence of the dependence of clinical benefit on biomarker classification is a priori unequivocal, personalized drug development needs to jointly investigate treatments and biomarkers in clinical trials. Motivated by the(More)
5006 Background: Bevacizumab (BV), a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor, has demonstrated clinical benefit in multiple tumor types. Activity in ovarian cancer (OC) has been reported in phase II studies in patients (pts) with recurrent disease. We now describe the activity/safety of BV in pts with(More)
In the past decade, the cost of drug development has increased significantly. The estimates vary widely but frequently quoted numbers are staggering-it takes 10-15 years and billions of dollars to bring a drug to patients. To a large extent this is due to many long, expensive and ultimately unsuccessful drug trials. While one approach to combat the low(More)
BACKGROUND Few data exist on the occurrence of metastatic basal cell carcinoma (mBCC). OBJECTIVE To identify all cases of mBCC in Denmark over a 14-year period. METHODS We searched the Danish National Patient Registry covering all Danish hospitals, the Danish Cancer Registry, the National Pathology Registry and the Causes of Death Registry during the(More)
AIMS To examine the possibility that monocyte esterase deficiency (MED) could be caused by exposure to organophosphates. METHODS Pseudocholinesterase, paraoxonase and arylesterase activities were measured in the serum and acetylcholinesterase activity was measured in the red cells of a group of monocyte esterase deficient subjects and compared with the(More)
We identify three properties of the standard oncology Phase I trial design or 3 + 3 design. We show that the standard design implicitly uses isotonic regression to estimate a maximum tolerated dose. We next illustrate the relationship between the standard design and a Bayesian design proposed by Ji et al. (2007). A slight modification to this Bayesian(More)
BACKGROUND Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma. In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to(More)
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