Daniel W. Bowles

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PURPOSE The objectives of the study were to evaluate the maximum tolerated dose (MTD), safety, pharmacodynamics, pharmacokinetics, and antitumor activity of PX-866 in patients with incurable cancers. EXPERIMENTAL DESIGN This was a phase I, open-label, dose-escalation study. Drug was administered orally once per day either on an intermittent (arm 1; days(More)
The EGF receptor (EGFR)-directed monoclonal antibody cetuximab is the only targeted therapy approved for the treatment of squamous cell carcinoma of the head and neck (HNSCC) but is only effective in a minority of patients. Epithelial-to-mesenchymal transition (EMT) has been implicated as a drug resistance mechanism in multiple cancers, and the EGFR and(More)
The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to(More)
PURPOSE This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway. EXPERIMENTAL DESIGN Patients with advanced, solid tumors received daily oral TAK-441 (50-1,600 mg/day); daily dose(More)
BACKGROUND This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours. METHODS PX-866 was administered at escalating doses (4-8 mg daily)(More)
PURPOSE The number of patients with cancer enrolling in phase I trials is expected to increase as these trials incorporate patient selection and exhibit greater efficacy in the era of targeted therapies. Despite the fact that people with advanced cancer often require a caregiver, little is known about the experience of caregivers of people enrolling in(More)
OBJECTIVE Stereotactic body radiotherapy (SBRT) is increasingly used to treat a variety of tumors, including head and neck squamous cell carcinoma (HNSCC) in the recurrent setting. While there are published data for re-irradiation using SBRT for HNSCC, there are limited data supporting its use as upfront treatment for locally advanced disease. STUDY(More)
Purpose: This first-inhuman study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investiga-tional inhibitor of the Hedgehog signaling pathway. Experimental Design: Patients with advanced, solid tumors received daily oral TAK-441 (50–1,600 mg/day); daily dose(More)