Alpelisib in combination with everolimus ± exemestane in solid tumours: Phase Ib randomised, open-label, multicentre study.

Background And Purpose: Combined mTORC1 inhibition with everolimus (EVE) and phosphatidylinositol 3-kinase catalytic subunit p110α blockade with alpelisib (ALP) has demonstrated synergistic efficacy in preclinical models and supports testing the combination of ALP and EVE in the clinical setting. The primary objective was to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of ALP in combination with EVE and in combination with EVE and exemestane (EXE) and subsequently assess safety, preliminary efficacy and effect of ALP on the pharmacokinetics of EVE and determine the magnitude of the drug-drug interaction.

Patients And Methods: Dose escalation phases were conducted in patients with advanced solid tumours and in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC).

Buparlisib plus carboplatin or lomustine in patients with recurrent glioblastoma: a phase Ib/II, open-label, multicentre, randomised study.

Background: Glioblastoma relapse is associated with activation of phosphatidylinositol 3-kinase (PI3K) signalling pathway. In preclinical studies, the pan-PI3K inhibitor buparlisib showed antitumour activity in glioma models.

Methods: This was a two-part, multicentre, phase Ib/II study in patients with recurrent glioblastoma pretreated with radiotherapy and temozolomide standard of care.

Phase I, open-label, multicentre study of buparlisib in combination with temozolomide or with concomitant radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Most glioblastoma tumours exhibit intrinsic phosphatidylinositol 3-kinase (PI3K) pathway activation. Preclinical in vitro and in vivo models suggest that buparlisib (an oral pan-PI3K inhibitor) can have an effect on glioblastoma directly and by enhancing the activity of radiation and of temozolomide.

Methods: This was a phase I, two-stage, multicentre, open-label, dose-escalation study of buparlisib in combination with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma.

A Phase Ib, open-label, dose-finding study of alpelisib in combination with paclitaxel in patients with advanced solid tumors.

Unlabelled: Phosphatidylinositol 3-kinase (PI3K) pathway activation is associated with resistance to paclitaxel in solid tumors. We assessed the safety and activity of alpelisib, an oral, selective PI3K p110α inhibitor, plus paclitaxel in patients with advanced solid tumors. This Phase Ib, multicenter, open-label, dose-finding study, with a planned dose-expansion phase of alpelisib once daily (QD) plus fixed-dose paclitaxel, recruited patients with advanced solid tumors.

[Was Claude Bernard an atheist?].

During his stay at Villefranche-sur-Saône College, Claude Bernard became acquainted with Ferdinand Donnet, appointed a short while ago, priest of the Parish. This priest became Cardinal and carried out his apostolate at Bordeaux for 47 years. 40 years after their meeting at Villefranche, Cardinal Donnet and Claude Bernard found again each other as "Sénateurs d'Empire" in Paris.

[The curve of the intraventricular pressure-volume relationships is not mono-exponential].

The graphic and statistic investigations have let us to assert that the right ventricular P/V relationship's curve is characterized by two successive segments: linear and exponential respectively. We have proposed an interpretation based on Roach's and Burton's works. Interest of information about this curve is double: 1) it is a function of the ventricular cavity volume; 2) it gives a general idea about the mode of ventricular filling.

[Tension-volume relationship of the wall of the isolated right ventricle].

The variations of tension on the wall of the isolated right verticle have been observed on 18 dogs. The Tension/Volume curve we got can be superimposed to that obtained by pressures. The wall of the right ventricle itself (the radius of the curve in the cavity and the wall-thickness) seems to vary only with the changes in its tension in a rather small part of the curve.

[Pressure-volume relationship in the right ventricle].

The curve of the pressure-volume relationships of the right ventricular cavity is not a mono-exponential one. It can be characterized by the presence of two successive segments: linear and exponential. The points that constitute the first of them could not be subjected to Starling's law.