A5048191133- PARP inhibition in cancer therapy
- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
- BRCA gene mutations in cancer
- Hormonal Regulation and Hypertension
- Ovarian cancer diagnosis and treatment
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- Prostate Cancer Treatment and Research
- Estrogen and related hormone effects
- Pituitary Gland Disorders and Treatments
- Lung Cancer Research Studies
- Alzheimer's disease research and treatments
- Brain Metastases and Treatment
- Cardiac and Coronary Surgery Techniques
- Adrenal Hormones and Disorders
- DNA Repair Mechanisms
- Pain Mechanisms and Treatments
- Pain Management and Opioid Use
- Acute Myocardial Infarction Research
- Dementia and Cognitive Impairment Research
- Health Systems, Economic Evaluations, Quality of Life
- Cancer therapeutics and mechanisms
- Cardiac, Anesthesia and Surgical Outcomes
- Caveolin-1 and cellular processes
Corcept Therapeutics (United States)
2021-2025
Pfizer (United States)
2015-2021
Tennessee Oncology
2011-2018
Texas Oncology
2018
Indiana University – Purdue University Indianapolis
2018
Indiana University Health
2018
Cornell University
2018
Memorial Sloan Kettering Cancer Center
2018
Janssen (United Kingdom)
2015
Butler Hospital
2015
Bapineuzumab, a humanized anti–amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease.
The poly(adenosine diphosphate-ribose) inhibitor talazoparib has shown antitumor activity in patients with advanced breast cancer and germline mutations BRCA1 BRCA2 ( BRCA1/2).We conducted a randomized, open-label, phase 3 trial which BRCA1/2 mutation were assigned, 2:1 ratio, to receive (1 mg once daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, vinorelbine continuous 21-day cycles). primary end point was progression-free survival,...
The majority of patients undergoing surgical treatment for ST-elevation myocardial infarction receive antifibrinolytic therapy to limit blood loss. This approach appears counterintuitive the accepted medical same condition--namely, fibrinolysis thrombosis. Despite this concern, no independent, large-scale safety assessment has been undertaken.In observational study involving 4374 revascularization, we prospectively assessed three agents (aprotinin [1295 patients], aminocaproic acid [883],...
Background— The risk of preoperative anemia in patients undergoing heart surgery has not been described precisely. Specifically, the impact low hemoglobin per se or combined with other factors on postoperative outcome is unknown. Thus, we determined effects and comorbidities adverse outcomes coronary artery bypass graft a large comprehensive multicenter study. Methods Results— Multicenter Study Perioperative Ischemia investigated 5065 at 70 institutions worldwide, collecting ≈7500 data...
Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated antitumor activity safety enzalutamide in locally advanced or metastatic AR-positive TNBC. Patients Methods Tumors were tested for immunohistochemistry assay optimized cancer; nuclear staining > 0% was considered positive. received 160 mg once per day until disease progression. The...
ContextAcute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However, no comprehensive data exist their associations with long-term mortality.ObjectiveTo contrast all-cause mortality patients undergoing coronary artery bypass graft (CABG) surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or antibleeding agent.Design,...
Abstract Purpose: registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. Experimental Design: Baseline characteristics patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, survival after CNS assessed. Associations between treatment evaluated. Results: Of the 1,012 who had confirmed tumors, 377 (37.3%) metastases. Compared no metastases, those younger...
1003 Background: The AR may be a therapeutic target for pts with androgen-driven TNBC. ENZA, potent inhibitor, is approved in men metastatic castration-resistant prostate cancer (mCRPC) and improves median PFS compared to bicalutamide mCRPC (15.7 vs 5.8 mos; HR 0.44; p<0.0001). Methods: MDV3100-11 was an open-label, Simon 2-stage study evaluating single agent ENZA advanced AR+ TNBC (AR >0% by IHC; NCT01889238). Pts could prescreened AR, have non-measurable bone disease unlimited prior...
<h3>Objective:</h3> To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using <sup>11</sup>C-Pittsburgh compound B (<sup>11</sup>C-PiB)-PET. <h3>Methods:</h3> Two phase 3 clinical trials, 1 each in apolipoprotein <i>APOE</i> ε4 carriers and noncarriers, were conducted patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change...
Abstract Background In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression-free survival (PFS) compared physician's choice of chemotherapy (PCT) in germline BRCA1/2-mutated HER2-negative advanced breast cancer (ABC). Herein, safety profile is explored detail. Materials and Methods Overall, 412 patients received ≥1 dose (n = 286) or PCT 126). Adverse events (AEs) were evaluated, including timing, duration, potential overlap selected...
Abstract Purpose: Chemotherapy resistance remains a major problem in many solid tumors, including breast, ovarian, and pancreatic cancer. Glucocorticoids are one potential driver of chemotherapy as they can mediate tumor progression via induction cell-survival pathways. We investigated whether combining the selective glucocorticoid receptor (GR) modulator relacorilant with taxanes enhance antitumor activity. Patients Methods: The effect on paclitaxel efficacy was assessed OVCAR5 cells vitro...
Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation relacorilant may restore chemosensitivity and enhance chemotherapy efficacy.This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, fallopian tube...
Background: Bapineuzumab, an anti-amyloid-β monoclonal antibody, was evaluated in two placebo-controlled trials APOE*ɛ4 carriers and noncarriers, respectively, with Alzheimer’s disease. Objectives: A volumetric magnetic resonance imaging substudy performed to determine if bapineuzumab altered brain volume rate of change. Methods: Bapineuzumab dosages included 0.5 mg/kg or 1.0 every 13 weeks for 78 weeks. Volumetric outcomes annualized brain, ventricular, mean hippocampal boundary shift...
Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction people with type 2 diabetes. In this prospective, observational study we assessed prevalence hypercortisolism, potential contributing factor to inadequate glucose control. Individuals diabetes and HbA1c 7.5%-11.5% (58-102 mmol/mol) on two or more medications without micro-/macrovascular complications taking blood pressure-lowering were screened 1-mg dexamethasone suppression test....
The androgen receptor (AR) is increasingly recognized as a potential biomarker for identifying subset of patients with possible hormonally driven triple-negative breast cancer (TNBC). However, its performance companion diagnostic remains elusive. Thus, we evaluated AR expression by immunohistochemistry in advanced TNBC before treatment the inhibitor enzalutamide.We optimized and validated assays prostate cell lines tissues using two commercial monoclonal antibodies (SP107 AR441). was then...
1083 Background: TNBC is a heterogeneous disease with multiple subtypes and drivers. ENZA, potent inhibitor of AR signaling, being tested in patients (pts) whose expresses (> 0%) by IHC (NCT01889238). However, expression may not confer ENZA sensitivity. Gene profiling was therefore explored to determine whether this could be superior predicting benefit from ENZA. Methods: Consent tissue for testing collected 404 pts. Next-Gen RNA-sequencing analysis performed on 175 samples: 122 samples came...
Immediate release (IR) hydromorphone has experienced significant misuse and abuse. An extended (ER) formulation been developed to provide sustained pain relief may reduce the likelihood for abuse by delaying absorption. In this double-blind, placebo-controlled, randomized, 2-part crossover study, potential of single oral doses ER (intact: 16-, 32-, 64-mg; milled: 8-mg) was compared with 8-mg IR placebo. After drug administration, subjects a history recreational opioid use completed series...
To assess the safety and efficacy of long-term repeated dosing OROS hydromorphone in chronic pain patients.This multicenter, open-label extension trial enrolled patients from three short-term trials.Fifty-six centers United States Canada.Adults with cancer or nonmalignant who were receiving stable doses (> = 8 mg/day). Three hundred eighty-eight enrolled, 106 completed at least 12 months therapy.OROS (individualized doses) was administered once daily.Safety (Brief Pain Inventory patient...
Abstract Purpose Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor 2-positive (HER2+) breast cancers. In vitro , AR inhibitors enhance antitumor activity trastuzumab, an anti-HER2 antibody, trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety enzalutamide, AR-signaling inhibitor, patients with advanced AR+ cancer previously treated trastuzumab. Methods Eligible had measurable or...
ABSTRACTObjective: To evaluate the safety, tolerability, and efficacy of once-daily osmotic controlled-release oral delivery system (OROS) hydromorphone in patients with chronic low back pain moderate-to-severe intensity.Research design methods: This was a 6-week, multicenter, nonrandomized, noncomparative, open-label, repeat-dose study (≥ 6 weeks) pain. The comprised three periods: prior opioid stabilization (2–7 days); OROS conversion, titration, stabilization (3–14 hydromorphone...
Background: The use of opioid analgesics for patients with chronic nonmalignant pain is becoming more widely accepted, and long-acting formulations are an important treatment option. Aim: To assess conversion to extended-release OROS® hydromorphone from previous stable agonist therapy in moderate-to-severe intensity. Methods: In this open-label multicentre trial, were stabilised on their before being switched at a ratio 5 : 1 (morphine sulphate equivalent hydrochloride). dose was titrated...
Abstract Background Talazoparib is a poly(adenosine diphosphate-ribose) polymerase inhibitor that causes death in cells with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations. Methods EMBRACA (NCT01945775) was randomized phase III study comparing efficacy, safety, and patient-reported outcomes (PROs) of talazoparib (1 mg) physician’s choice chemotherapy (PCT: capecitabine, eribulin, gemcitabine, vinorelbine) locally advanced metastatic germline BRCA1/2 (gBRCA1/2) mutation....