32 research outputs found
Decisional conflict after deciding on potential participation in early phase clinical cancer trials: Dependent on global health status, satisfaction with communication, and timing
Realizing better doctor-patient dialogue about choices in palliative care and early phase clinical trial participation: towards an online value clarification tool (OnVaCT)
Influence of enzalutamide on cabazitaxel pharmacokinetics: A Drug–Drug interaction study in metastatic castration-resistant prostate cancer (mCRPC) patients
Purpose: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, that is, enzalutamide and abiraterone, is currently being explored. Because enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug–drug interaction needs to be investigated. Experimental Design: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m2). Patients were studied for three consecutive cabazitaxel cycles. Enzalutamide (160 mg once daily) was administered concomitantly after the first cabazitaxel cycle, during 6 weeks. Primary endpoint was the difference in mean area under the curve (AUC) between the first (cabazitaxel monotherapy) and third cabazitaxel cycle, when enzalutamide was added. Results: A potential clinically relevant 22% (95% CI, 9%–34%; P ¼ 0.005) reduction in cabazitaxel exposure was found with concomitant enzalutamide use. The geometric mean AUC0–24h of cabazitaxel was 181 ngh/mL (95% CI, 150–219 ngh/mL) in cycle 3 and 234 ngh/mL (95% CI, 209–261 ngh/mL) in cycle 1. This combination did not result in excessive toxicity, whereas PSA response was promising. Conclusions: We found a significant decrease in cabazitaxel exposure when combined with enzalutamide. In an era of clinical trials on combination strategies for mCRPC, it is important to be aware of clinically relevant drug–drug interactions. Because recent study results support the use of a lower standard cabazitaxel dose of 20 mg/m2, the clinical relevance of this interaction may be substantial, because the addition of enzalutamide may result in subtherapeutic cabazitaxel exposure
High-throughput isolation of circulating tumor DNA
The emerging interest in circulating tumor DNA (ctDNA) analyses for clinical
trials has necessitated the development of a high-throughput method for fast,
reproducible, and efficient isolation of ctDNA. Currently, the majority of
ctDNA studies use the manual QIAamp (QA) platform to isolate DNA from
blood. The purpose of this study was to compare two competing automated
DNA isolation platforms [Maxwell (MX) and QIAsymphony (QS)] to the current ‘gold standard’ QA to facilitate high-throughput processing of samples in
prospective trials. We obtained blood samples from healthy blood donors and
metastatic cancer patients for plasma isolation. Total cell-free DNA (cfDNA)
quantity was assessed by TERT quantitative PCR. Recovery efficiency was
investigated by quantitative PCR analysis of spiked-in synthetic plant DNA.
In addition, a b-actin fragmentation assay was performed to determine the
amount of contamination by genomic DNA from lysed leukocytes. ctDNA
quality was assessed by digital PCR for somatic variant detection. cfDNA
quantity and recovery efficiency were lowest using the MX platform, whereas
QA and QS showed a comparable performance. All platforms preferentially
isolated small (136 bp) DNA fragments over large (420 and 2000 bp) DNA
fragments. Detection of the number variant and wild-type molecules was most
comparable between QA and QS. However, there was no significant difference
in variant allele frequency comparing QS and MX to QA. In summary, we
show that the QS platform has comparable performance to QA, the ‘gold
standard’, and outperformed the MX platform depending on the readout
used. We conclude that the QS can replace the more laborious QA platform,
especially when high-throughput cfDNA isolation is needed
Circulating tumor cell enumeration and characterization in metastatic castration-resistant prostate cancer patients treated with cabazitaxel
(1) Background: Markers identifying which patients with metastatic, castration-resistant prostate cancer (mCRPC) will benefit from cabazitaxel therapy are currently lacking. Therefore, the aim of this study was to identify markers associated with outcome to cabazitaxel therapy based on counts and gene expression profiles of circulating tumor cells (CTCs). (2) Methods: From 120 mCRPC patients, CellSearch enriched CTCs were obtained at baseline and after 6 weeks of cabazitaxel therapy. Furthermore, 91 genes associated with prostate cancer were measured in mRNA of these CTCs. (3) Results: In 114 mCRPC patients with an evaluable CTC count, the CTC count was independently associated with poor progression-free survival (PFS) and overall survival (OS) in multivariable analysis with other commonly used variables associated with outcome in mCRPC (age, prostate specific antigen (PSA), alkaline phosphatase, lactate dehydrogenase (LDH), albumin, hemoglobin), together with alkaline phosphatase and hemoglobin. A five-gene expression profile was generated to predict for outcome to cabazitaxel therapy. However, even though this signature was associated with OS in univariate analysis, this was not the case in the multivariate analysis for OS nor for PFS. (4) Conclusion: The established five-gene expression profile in CTCs was not independently associated with PFS nor OS. However, along with alkaline phosphatase and hemoglobin, CTC-count is independently associated with PFS and OS in mCRPC patients who are treated with cabazitaxel
AC loss in superconducting tapes and cables
The present study discusses the AC loss in high-temperature superconductors. Superconducting materials with a relatively high critical temperature were discovered in 1986. They are presently developed for use in large-scale power-engineering devices such as power-transmission cables, transformers and electric motors. The alternating magnetic field in these devices causes energy dissipation (AC loss) despite the zero resistance of the superconductor in stationary circumstances. The dissipated heat must be removed from the low-temperature environment by a refrigerator, whose power consumption is 10-20 times the AC loss. The study is intended to ascertain whether high-temperature superconductors can be produced with an AC loss low enough to compete with copper. The study focuses on the material Bi-2223, which is presently produced in the form of long flexible tapes, comprising thin superconducting filaments embedded in a silver matrix. The AC loss is measured by magnetic, electric and calorimetric methods, which are adapted for the investigation of hightemperature superconducting tapes
Maternidad tras una muerte perinatal
La nueva gestación tras una muerte perinatal está llena de dudas, miedos e inseguridades, y es una situación que va a suponer un desgaste fÃsico y emocional para la familia, especialmente para la mujer. Esta gestación se caracteriza por un aumento de la ansiedad, que puede continuar después del nacimiento y manifestarse mediante conductas de sobreprotección del nuevo hijo. Las matronas deben conocer las posibles respuestas emocionales de la mujer y proporcionar cuidados y apoyo especÃficos durante el embarazo, parto y puerperio, en función de las necesidades individuales de cada familia