Is Higher Docetaxel Clearance in Prostate Cancer Patients Explained by Higher CYP3A? An In Vivo Phenotyping Study with Midazolam.

Patients with prostate cancer (PCa) have a lower docetaxel exposure for both intravenous (1.8-fold) and oral administration (2.4-fold) than patients with other solid cancers, which could influence efficacy and toxicity.

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands.

Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population.

Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients.

Objectives: Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C) of abiraterone. Patients with a plasma C below the target of 8.

Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors.

Background: The phase 3 trial CA184-043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate cancer (mCRPC) who had received docetaxel previously. In a prior analysis, the trial's primary endpoint (overall survival [OS]) was not improved significantly.

Objective: To report the final analysis of OS.

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer: Results from the Dutch Castration-resistant Prostate Cancer Registry.

Background: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2).

Objective: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2.

Design, Setting, And Participants: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI).

Second-Line Cabazitaxel Treatment in Castration-Resistant Prostate Cancer Clinical Trials Compared to Standard of Care in CAPRI: Observational Study in the Netherlands.

Background: Cabazitaxel has been shown to improve overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel in the TROPIC trial. However, trial populations may not reflect the real-world population. We compared patient characteristics and outcomes of cabazitaxel within and outside trials (standard of care, SOC).

Neutropenia and docetaxel exposure in metastatic castration-resistant prostate cancer patients: A meta-analysis and evaluation of a clinical cohort.

The incidence of neutropenia in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel has been reported to be lower compared to patients with other solid tumors treated with a similar dose. It is suggested that this is due to increased clearance of docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid tumors by conducting a meta-analysis, (2) evaluate the incidence of neutropenia in patients with mCRPC vs other solid tumors in a clinical cohort, and (3) discuss potential clinical consequences.

Randomized Phase III Study to Assess Efficacy and Safety of Adjuvant CAPOX with or without Bevacizumab in Patients after Resection of Colorectal Liver Metastases: HEPATICA study.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs.

The Effects of Enzalutamide Monotherapy on Multiparametric 3T MR Imaging in Prostate Cancer.

The effects of enzalutamide monotherapy on prostate tumor downsizing and multiparametric MRI are currently unknown. Here we present the first case in literature of a patient with high-grade prostate cancer who underwent 3 months of neoadjuvant enzalutamide, for which the effects on mpMRI and histology were determined. Tumor size reduction and downstaging were noted.

CAST: A retrospective analysis of cabazitaxel and abiraterone acetate sequential treatment in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel.

Cabazitaxel and abiraterone have both received approval for treating metastatic castrate-resistant prostate cancer (mCRPC) patients after first-line docetaxel therapy. In the cabazitaxel and abiraterone sequential treatment (CAST) study, the clinical outcome of docetaxel-treated mCRPC patients treated sequentially with both cabazitaxel and abiraterone was studied. Data were collected retrospectively from mCRPC patients at 12 hospitals across the Netherlands who initiated cabazitaxel and/or abiraterone before December 2012.

Fibroblast growth factor receptor 3 activation plays a causative role in urothelial cancer pathogenesis in cooperation with Pten loss in mice.

Although somatic mutations and overexpression of the tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) are strongly associated with bladder cancer, evidence for their functional involvement in the pathogenesis remains elusive. Previously we showed that activation of Fgfr3 alone is not sufficient to initiate urothelial tumourigenesis in mice. Here we hypothesize that cooperating mutations are required for Fgfr3-dependent tumourigenesis in the urothelium and analyse a mouse model in which an inhibitor of Pi3k-Akt signalling, Pten, is deleted in concert with Fgfr3 activation (UroIICreFgfr3(+/) (K644E) Pten(flox) (/flox)).

Induction chemotherapy followed by surgery in node positive bladder cancer.

Objective: To evaluate the outcome and prognostic factors of patients with node positive bladder cancer (NPBC), who were eligible for surgery and treated with induction chemotherapy.

Methods: All consecutive patients with NPBC, who were treated with at least 2 cycles of induction chemotherapy and initially scheduled for surgery, between 1990 and 2012, were identified from an institutional bladder cancer database. Induction chemotherapy consisted of MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or gemcitabine with cisplatin (Gem/Cis) or carboplatin (Gem/Carbo).

FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer.

Purpose: We evaluated FDG-positron emission tomography/computerized tomography for monitoring the response of pelvic lymph node metastasis to neoadjuvant chemotherapy for bladder cancer. We compared this to contrast enhanced computerized tomography.

Materials And Methods: Included in study were 19 consecutive patients with lymph node positive bladder cancer who underwent FDG-positron emission tomography/computerized tomography and contrast enhanced computerized tomography before and after a median of 4 cycles (range 2 to 4) of neoadjuvant chemotherapy between September 2011 and April 2012.

A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment.

Background: About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation.