Center-Specific Modeling Predicts Cancer Trial Accrual More Accurately Than Investigators and Random Effects Modeling at 16 Cancer Centers.

Purpose: Clinical trials often exceed their anticipated enrollment periods, and study sites often do not meet accrual goals. We previously reported the development and validation of a single-site accrual prediction model. Here, we describe the expansion of this methodology at 16 cancer centers (CCs) and compare an overall model versus site-specific models.

Development and Validation of a Clinical Trial Accrual Predictive Regression Model at a Single NCI-Designated Comprehensive Cancer Center.

Background: Clinical study sites often do not achieve anticipated accrual to clinical trials, wasting critical patient, material, and human resources. The expensive and extensive process to bring a drug to approval highlights the need to streamline clinical pipeline processes. We sought to create a predictive accrual model to be used when considering clinical trial activation at the level of the individual site.

Quality-adjusted time without symptoms or toxicity (Q-TWiST): patient-reported outcome or mathematical model? A systematic review in cancer.

Objective: Successful cancer treatment is defined as an increase in overall survival and/or progression-free survival. Despite their importance, these metrics omit patient quality of life. Quality-adjusted time without symptoms or toxicity (Q-TWiST) was developed to adjust survival gained, accounting for quality of life.

Clinical and economic burden of Richter syndrome in inpatient cases of chronic lymphocytic leukemia within the United States, 2001-2010.

Richter syndrome (RS) is an aggressive transformation of chronic lymphocytic leukemia (CLL) characterized by poor prognoses. The purpose of this study was to assess clinical and economic characteristics of RS within inpatient hospital settings in the United States from 2001 to 2010. This retrospective cohort study employed data from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project.

Identification of thioredoxin-interacting protein 1 as a hypoxia-inducible factor 1alpha-induced gene in pancreatic cancer.

Objective: To investigate the expression of thioredoxin-interacting protein (TXNIP) during hypoxia and its dependency on hypoxia-inducible factor 1alpha (HIF-1alpha) in pancreatic cancer cell lines.

Methods: MiaPaCa-2 pancreatic cancer cells were transiently transfected with siRNA to HIF-1alpha and TXNIP protein measured after growth in normoxia or hypoxia. In addition, HIF-1alpha dependency was assessed by transiently transfecting MiaPaCa-2 pancreatic cancer cells with HIF-1alpha with a mutated oxygen degradation domain resulting in stable HIF-1alpha expression in normoxic conditions.

The antitumor agent imexon activates antioxidant gene expression: evidence for an oxidative stress response.

Purpose: The aim of this study was to identify biomarkers that may be predictive for the clinical activity of the redox-active antitumor agent imexon.

Experimental Design: cDNA microarray and quantitative real-time PCR were used to identify global changes in gene expression in peripheral blood mononuclear cells (PBMC) collected from patients treated with imexon during a phase I trial. Electrophoretic mobility shift assays and Western blot analysis were done using the RPMI8226 myeloma cell line grown in vitro and PBMCs treated ex vivo to investigate the molecular mechanism responsible for these gene changes.

The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma.

Thioredoxin-1 (Trx-1) is a small redox protein that is overexpressed in many human tumors, where it is associated with aggressive tumor growth and decreased patient survival. Trx-1 is secreted by tumor cells and is present at increased levels in the plasma of cancer patients. PX-12 is an irreversible inhibitor of Trx-1 currently in clinical development as an antitumor agent.

The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts.

Epidermal growth factor receptor (EGFR) inhibitors such as gefitinib show antitumor activity in a subset of non-small cell lung cancer (NSCLC) patients having mutated EGFR. Recent work shows that phosphatidylinositol-3-kinase (PI3-K) is coupled to the EGFR only in NSCLC cell lines expressing ErbB-3 and that EGFR inhibitors do not inhibit PI3-K signaling in these cells. The central role PI3-K plays in cell survival suggests that a PI3-K inhibitor offers a strategy to increase the antitumor activity of EGFR inhibitors in resistant NSCL tumors that do not express ErbB-3.

The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging.

Purpose: The purpose of this study was to use dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to measure changes in tumor xenograft permeability produced by the antitumor thioredoxin-1 (Trx-1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) and to assess the relationship to Trx-1 and vascular endothelial growth factor (VEGF) levels.

Experimental Design: DCE-MRI was used to monitor the dynamics of gadolinium-diethylenetriaminepentaacetic acid coupled bovine serum albumin as a macromolecular contrast reagent to measure hemodynamic changes in HT-29 human colon xenografts in immunodeficient mice treated with PX-12. Blood vessel permeability was estimated from the slope of the enhancement curves, and tumor vascular volume fraction from the ordinate.