Clinical Pharmacy Initiatives Contribute to the Excellent Efficacy of the Dabrafenib/Trametinib Combination for Iodine-Refractory Thyroid Carcinoma: A Case Report.

A 76-year-old female patient presented with an iodine-refractory papillary thyroid carcinoma (PTC), diagnosed eight years earlier, with several lymph node recurrences requiring successive surgeries. Fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) imaging revealed a new unresectable loco-regional recurrence. The patient was diagnosed with a somatic BRAF V600E mutation.

Attributes for a discrete-choice experiment on preferences of patients for oncology pharmacy consultations.

Purpose: To ensure the safe use of oral anticancer drugs, oncology pharmacy consultations (OPCs) have been established in France. They are conditioned by the needs, expectations, and involvement of the patients in their care. Thus, it is essential to elicit their preferences.

Combining Three Tyrosine Kinase Inhibitors: Drug Monitoring Is the Key.

A combination of tyrosine kinase inhibitors (TKIs) is likely to be a therapeutic option for numerous oncological situations due to high frequency of oncogenic addiction and progress in precision oncology. Non-small cell lung cancer (NSCLC) represents a subtype of tumors for which oncogenic drivers are frequently involved. To the best of our knowledge, we report the first case of a patient treated with three different TKIs.

[Unusual association of BRAF and MEK inhibitors: Clinical response of metastatic melanoma treated with dabrafenib-cobimetinib].

Despite the efficacy of targeted therapies in melanoma, the management of adverse events with BRAFi and MEKi (inhibitors) is one of the limits of these treatments. Close monitoring is required to ensure efficacy and patient safety. In this case study, we report a patient treated for metastatic melanoma with an unusual and innovative combination of dabrafenib (BRAFi) and cobimetinib (MEKi), to manage pyrexia, and lead to complete remission for 19 months.

Case report: Liquid biopsy, the sooner the better?

The detection of circulating tumor DNA (ctDNA) by liquid biopsy is taking an increasing role in thoracic oncology management due to its predictive and prognostic value. For non-small cell lung cancer, it allows the detection of molecular mutations that can be targeted with tyrosine kinase inhibitors (TKIs). We report the case of a patient with life-threatening hepatocellular failure and thrombotic microangiopathy at the diagnosis.

PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1.

Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level.

Impact of pharmacist consultation at clinical trial inclusion: an effective way to reduce drug-drug interactions with oral targeted therapy.

Purpose: Pharmacist consultation is unfrequently performed in oncology clinical trials that include patients who often have many co-treatments increasing the risk of drug-drug interactions (DDI). The aim of this study was to determine whether best possible medication history (BPMH) by hospital pharmacist at inclusion and therapeutic drug monitoring could be used for DDI risk evaluation and for current oral targeted therapy management.

Methods: A prospective clinical trial (ALCINA 2, NCT04025541) was carried out in metastatic breast cancer cohort treated by palbociclib to conduct pharmacokinetics-toxicity correlation study.

Therapeutic Bayesian monitoring of sunitinib in two patients with impaired absorption or elimination.

What Is Known And Objective: Sunitinib pharmacokinetics can be influenced by the physio-pathological conditions of individual patients. Therapeutic drug monitoring (TDM) helps to optimize efficacy and reduce the risk of adverse effects. We report on the use of Bayesian analysis to optimize sunitinib blood levels.

Alpelisib for the treatment of -mutated, hormone receptor-positive, HER2-negative metastatic breast cancer.

: Two-thirds of advanced breast cancers are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-). Gene mutations in , encoding the PI3K catalytic subunit alpha of phosphatidyl-inositol 3-kinase (PI3K), are a frequent event in this population and are implicated in hormone therapy resistance. Alpelisib is a PI3K-alpha inhibitor and is the first PI3K inhibitor approved, in association with fulvestrant, by the FDA and EMA, based on improved progression-free survival (PFS) versus fulvestrant alone in a randomized phase III trial in HR+/HER2-, -mutated tumors following progression on/after HT.

[Securing the patient's care path receiving oral anticancer therapy: Experimentation around a pharmaceutical hospital-to-community liaison].

Due to the increasing prescription of oral anticancer therapies, the inpatient care pathway has shifted to an outpatient care pathway. This transformation requires an interdisciplinary coordination to provide a continuum of care and ensure therapeutic monitoring, as well as patient safety. To better support patients on oral anticancer therapies, a task group named "hospital-to-community pharmacist coordination" has been set up to create tools aiming at standardising the information exchanged between ambulatory and hospital pharmacists.

Cancer Immunotherapy Dosing: A Pharmacokinetic/Pharmacodynamic Perspective.

Immune check-point inhibitors are drugs that are markedly different from other anticancer drugs because of their indirect mechanisms of antitumoral action and their apparently random effect in terms of efficacy and toxicity. This marked pharmacodynamics variability in patients calls for reconsidering to what extent approved dosing used in clinical practice are optimal or whether they should require efforts for customization in outlier patients. To better understand whether or not dosing could be an actionable item in oncology, in this review, preclinical and clinical development of immune checkpoint inhibitors are described, particularly from the angle of dose finding studies.

Liquid chromatography-tandem mass spectrometric assay for the quantification of CDK4/6 inhibitors in human plasma in a clinical context of drug-drug interaction.

The CDK4/6 inhibitors palbociclib and ribociclib are kinase inhibitors used in association with hormonal therapy for the management of patients with metastatic breast cancer. Like most kinase inhibitors, therapeutic drug monitoring may be used for personalize their dosage. To this aim, we developed and validated a sensitive and specific HPLC-MS/MS method for palbociclib and ribociclib quantification in blood samples.

'Low-Salt' Bread as an Important Component of a Pragmatic Reduced-Salt Diet for Lowering Blood Pressure in Adults with Elevated Blood Pressure.

Reformulation of bread in terms of salt content remains an important measure to help achieve a reduction in salt intake in the population and for the prevention of hypertension and elevated blood pressure (BP). Our fundamental studies on the reduction of salt on dough and bread characteristics showed that wheat breads produced with 0.3 g salt/100 g ("low-salt") were found to be comparable quality to that produced with the typical level of salt (1.

Challenging BRAF/EGFR co-inhibition in NSCLC using sequential liquid biopsies.

Objectives: There is some controversy surrounding theBRAF mutation in patients with lung adenocarcinomas. Although the BRAF mutation is sensitive to BRAF inhibitors, the efficiency of these inhibitors on patients harboring an EGFR/EGFR/BRAF pattern remains unknown.

Materials And Methods: Here, we presented the case of a patient with initial response followed by progression on osimertinib.

Pharmacist intervention to detect drug adverse events on admission to the emergency department: Two case reports of neuroleptic malignant syndrome.

What Is Known And Objective: Neuroleptic malignant syndrome (NMS) is a rare but severe adverse effect of antipsychotic drugs.

Case Description: We report two cases of NMS highlighted by clinical pharmacists in an emergency unit during summer. One of them was fatal.

Wheat germ supplementation of a low vitamin E diet in rats affords effective antioxidant protection in tissues.

Background: Oxidative stress is implicated in the etiology of many diseases, but most of clinical trials failed to demonstrate beneficial effects of antioxidant supplementation.

Methods: In the present experiment, we assessed the mean-term effect of wheat germ supplementation, as a dietary source of vitamin E, on antioxidant protection in rat.

Results: Feeding rats a 20% wheat germ diet significantly increased plasma and liver vitamin E levels, compared to the low vitamin E basal diet.

Parameters controlling the glycaemic response to breads.

Bread is one of the most widely consumed staple foods worldwide. White-wheat bread, largely consumed in France, is made from highly refined flour, which leads to a low nutrient density. Due to a highly porous structure and gelatinised starch, it is easily broken down during digestion, leading to a rapid increase of glucose released into the bloodstream.

Wheat lipoxygenase activity induces greater loss of carotenoids than vitamin E during breadmaking.

The current study was undertaken to provide solutions to optimize the unsaponifiable antioxidants content of bread. We report a complete description of changes in wheat carotenoids and vitamin E content from grain to bread and highlight the most important processing steps affecting their level in wheat bread. Major carotenoids losses occurred during kneading.

New data on the bioavailability of bread magnesium.

Whole cereal products are the main source of magnesium in human nutrition. Even if wholemeal bread is an important source of Mg, it also contains considerable amounts of phytic acid (PA), a natural chelator that lowers the absorption of trace elements such as Fe or Zn as well as Ca or Mg in cereal products. Significant Mg bioavailability improvement in bread could be supplied by the choice of raw materials and the baking processes of cereals.

Moderate decrease of pH by sourdough fermentation is sufficient to reduce phytate content of whole wheat flour through endogenous phytase activity.

Whole wheat bread is an important source of minerals but also contains considerable amounts of phytic acid, which is known to impair their absorption. An in vitro trial was performed to assess the effect of a moderate drop of the dough pH (around 5.5) by way of sourdough fermentation or by exogenous organic acid addition on phytate hydrolysis.

The bioavailability of ferulic acid is governed primarily by the food matrix rather than its metabolism in intestine and liver in rats.

The physiologic importance of ferulic acid (FA), and notably its antioxidant properties, depends upon its availability for absorption and subsequent interaction with target tissues. Because FA is widely present in cereals, the aim of the present study was to investigate its intestinal and hepatic metabolism in rats by in situ intestinal perfusion model (from 10 to 50 nmol/min), and its bioavailability in supplemented diets (from 10 to 250 micromol/d) or in a complex cereal matrix, i.e.