Results of the first international quality control programme for oral targeted oncolytics.

Aims: With the rising number of oral targeted oncolytics and growing awareness of the benefits of therapeutic drug monitoring (TDM) within the field of oncology, it is expected that the requests for quantifying concentrations of these drugs will increase. It is important to (cross-)validate available assays and ensure its quality, as results may lead to altered dosing recommendations. Therefore, we aimed to evaluate the performance of laboratories measuring concentrations of targeted oral oncolytics in a one-time international quality control (QC) programme.

Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose Recommendations.

Background: The clinical outcomes of busulfan-based conditioning regimens for hematopoietic cell transplantation (HCT) have been improved by personalizing the doses to target narrow busulfan plasma exposure. An interlaboratory proficiency test program for the quantitation, pharmacokinetic modeling, and busulfan dosing in plasma was developed. Previous proficiency rounds (ie, the first 2) found that 67%-85% and 71%-88% of the dose recommendations were inaccurate, respectively.

Quality Control of Busulfan Plasma Quantitation, Modeling, and Dosing: An Interlaboratory Proficiency Testing Program.

Background: Personalizing busulfan doses to target a narrow plasma exposure has improved the efficacy and lowered the toxicity of busulfan-based conditioning regimens used in hematopoietic cell transplant. Regional regulations guide interlaboratory proficiency testing for busulfan concentration quantification and monitoring. To date, there have been no comparisons of the busulfan pharmacokinetic modeling and dose recommendation protocols used in these laboratories.

Therapeutic drug monitoring of tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric dried blood spot sampling device.

Aims: Tacrolimus and mycophenolic acid dosing after renal transplantation is individualized through therapeutic drug monitoring (TDM). Home-based dried blood spot (DBS) sampling has the potential to replace conventional TDM sampling at the clinic. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed to quantify tacrolimus and mycophenolic acid in DBS and clinically validated for abbreviated area under the concentration-time curve (AUC) monitoring using an innovative volumetric DBS sampling device.

Excision Repair Cross-Complementation group 1 (ERCC1) C118T SNP does not affect cellular response to oxaliplatin.

Aims: ERCC1 is involved in the repair of oxaliplatin-induced DNA damage. Studies for the association of the C118T SNP with clinical response to treatment with platinum drugs have rendered inconsistent results. We investigated the ERCC1 C118T SNP with respect to overall and progression-free survival in patients with advanced colorectal cancer (ACC) treated with oxaliplatin and in vitro DNA repair capacity after oxaliplatin exposure.

Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients.

Purpose: Oxaliplatin is detoxified by conjugation to glutathione via the enzyme Glutathione-S-transferase pi (GSTP1). The aim of this study is to investigate the association of GSTP1 Ile105Val genetic polymorphism with oxaliplatin efficacy and toxicity in advanced colorectal cancer (ACC) patients.

Experimental Design: A total of 91 ACC patients received capecitabine and oxaliplatin (CAPOX) as a part of a multicentre phase-III study of the Dutch Colorectal Cancer Group.