A case for the use of receiver operating characteristic analysis of potential clinical efficacy biomarkers in advanced renal cell carcinoma.

Aim: Assess patient-level utility of suggested pretreatment biomarkers of sunitinib in advanced renal cell carcinoma.

Patients & Methods: Kaplan-Meier analysis of data from a randomized, Phase II study (n = 292) suggested baseline predictive value for circulating soluble Ang-2 and MMP-2 and HIF-1α percentage of tumor expression. Using this dataset, the sensitivity, specificity and area under the curve (AUC) were calculated, using receiver operating characteristic (ROC) curves.

Genotype Correlations With Blood Pressure and Efficacy From a Randomized Phase III Trial of Second-Line Axitinib Versus Sorafenib in Metastatic Renal Cell Carcinoma.

Background: In the phase III axitinib second-line (AXIS) trial, axitinib significantly prolonged progression-free survival (PFS) versus sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC). Analyses of associations between germline single-nucleotide polymorphisms (SNPs) and outcomes are reported.

Patients And Methods: DNA samples from blood were genotyped using TaqMan allelic discrimination.

Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma.

Purpose: Sunitinib is a first-line advanced renal cell carcinoma (RCC) standard of care. In a randomized phase II trial comparing sunitinib treatment schedules, separate exploratory biomarker analyses investigated the correlations of efficacy with selected serum, germ line single-nucleotide polymorphism (SNP), or tumor markers.

Methods: Advanced RCC patients received first-line sunitinib 50 mg/day on the approved 4-week-on-2-week-off schedule (n = 146) or 37.

Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

Mantle cell lymphoma (MCL) carries an unfavorable prognosis and requires new treatment strategies. The associated t(11:14) translocation results in enhanced cyclin D1 expression and cyclin D1-dependent kinase activity to promote cell-cycle progression. A pharmacodynamic study of the selective CDK4/6 inhibitor PD0332991 was conducted in 17 patients with relapsed disease, using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and 3-deoxy-3[(18)F]fluorothymidine (FLT) positron emission tomography (PET) to study tumor metabolism and proliferation, respectively, in concert with pre- and on-treatment lymph node biopsies to assess retinoblastoma protein (Rb) phosphorylation and markers of proliferation and apoptosis.

Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours.

This phase I study (ClinicalTrials.gov ID: NCT00424632) evaluated the safe dose, pharmacokinetics, and pharmacodynamics of the aurora kinase A and B inhibitor, PF-03814735. Patients with advanced solid tumours received oral, once-daily (QD) PF-03814735 on Schedule A: days 1-5 (5-100mg); or Schedule B: days 1-10 (40-60mg) of 21-day cycles.

Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial.

Background: In an earlier 21-day, placebo-controlled trial, ziprasidone was efficacious in improving symptoms of mania and was well tolerated. To confirm these results, a similarly designed 21-day trial was conducted.

Methods: Inpatients with bipolar I disorder, manic or mixed, were randomized to ziprasidone (40 to 80 mg BID) or placebo.