High-Dose Intermittent Treatment with the Multikinase Inhibitor Sunitinib Leads to High Intra-Tumor Drug Exposure in Patients with Advanced Solid Tumors.

Patients with advanced cancer refractory to standard treatment were treated with sunitinib at a dose of 300 mg once every week (Q1W) or 700 mg once every two weeks (Q2W). Tumor, skin and plasma concentrations were measured and immunohistochemical staining for tumor cell proliferation (TCP), microvessel density (MVD) and T-cell infiltration was performed on tumor biopsies before and after 17 days of treatment. Oral administration of 300 mg sunitinib Q1W or 700 mg Q2W resulted in 19-fold (range 5-35×) and 37-fold higher (range 10-88×) tumor drug concentrations compared to parallel maximum plasma drug concentrations, respectively.

High-dose administration of tyrosine kinase inhibitors to improve clinical benefit: A systematic review.

Background: Innovative strategies to fully exploit the antitumor activity of multitargeted tyrosine kinase inhibitors (TKIs) are urgently needed. Higher concentrations of TKIs at their target site, i.e.

Correction to: [89Zr]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer.

Missing Electronic Supplementary Materials.

[Zr]Zr-cetuximab PET/CT as biomarker for cetuximab monotherapy in patients with RAS wild-type advanced colorectal cancer.

Purpose: One-third of patients with RAS wild-type mCRC do not benefit from anti-EGFR monoclonal antibodies. This might be a result of variable pharmacokinetics and insufficient tumor targeting. We evaluated cetuximab tumor accumulation on [Zr]Zr-cetuximab PET/CT as a potential predictive biomarker and determinant for an escalating dosing strategy.

Decalcification of Breast Cancer Bone Metastases With EDTA Does Not Affect ER, PR, and HER2 Results.

In metastatic breast cancer (MBC), expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) guides treatment selection. In case of bone-only metastatic disease, ER, PR, and HER2 status assessment may be hampered by decalcification. We aimed to determine the optimal decalcification method, and to study discordance of receptor expression between paired primary breast tumors and optimally decalcified bone metastases.

Phase I Dose-Escalation Study of Once Weekly or Once Every Two Weeks Administration of High-Dose Sunitinib in Patients With Refractory Solid Tumors.

Purpose: Dose and schedule optimization of treatment with tyrosine kinase inhibitors is of utmost importance. On the basis of preclinical data, a phase I clinical trial of once weekly or once every 2 weeks administration of high-dose sunitinib in patients with refractory solid malignancies was conducted.

Patients And Methods: Patients with advanced cancer refractory to standard treatment were eligible.

The 'morning dip' in antimicrobial appropriateness: circumstances determining appropriateness of antimicrobial prescribing.

Objectives: Quality of care has been shown to vary depending on the time of day or day of the week and depending on caregivers' gender and experience. We aimed to study how these factors influence quality of antimicrobial prescribing.

Methods: Prospective point-prevalence surveys were performed to determine the association between the above-mentioned prescription factors and antimicrobial appropriateness.

Trends in incidence, treatment and survival of small bowel adenocarcinomas between 1999 and 2013: a population-based study in The Netherlands.

Background: We conducted a population-based study to establish the incidence, treatment and overall survival over time of patients with small bowel adenocarcinoma.

Material And Methods: All patients diagnosed with small bowel adenocarcinoma in the Netherlands between 1999 and 2013 were included (n = 1775). Age-standardized incidence rates were calculated per 100 000 person-years using the European standardized population rate.