In Spain luminal metastatic Breast Cancer accounts for more than 3000 deaths yearly. Ribociclib+letrozole has shown efficacy on prolonging progression free survival (PFS) vs placebo+letrozol in two ...phase 3 trials. However, data on efficacy and tolerability is lacking for a broader population. We present interim data from CompLEEment-1, an ongoing, open-label, phase 3b trial evaluating ribociclib+letrozole as first-line endocrine therapy in an expanded population of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC).
Patients treated with ≤1line of prior chemotherapy and no prior endocrine therapy for advanced disease received ribociclib 600mg/day (3-weeks-on/1week-off) + letrozole (2.5mg/day; plus monthly goserelin or leuprolide in men and premenopausal women). The primary objective was safety and tolerability. Here we report a sub-analysis of CompLEEment-1 for the Spanish population.
526 patients were evaluated over a median follow-up of 10.3 months. Baseline characteristics indicated a diverse population with median age of 55.6 years (range 24-85); 0.8% of patients were male, 34.6% female pre-menopausal and 64.6% female post-menopausal. 71% had visceral metastasis, in 8 cases at the CNS. 55.9% had measurable disease at baseline. The rate of all-grade and grade ≥ 3 treatment-related adverse events (AEs) was 98.5% and 70.0%, respectively. Treatment-related serious AEs occurred in 12.2% of patients. All-grade and grade ≥ 3 AEs leading to ribociclib discontinuation occurred in 13.7% and 8.2% of patients, respectively. Rates of≥3 AEs of special interest (AESI) were 59.5% for neutropenia, 6.8% for increased alanine aminotransferase, 4.8% for increased aspartate aminotransferase, and 0.6% for QTcF prolongation. Patient health-related quality of life was maintained versus baseline.
Initial results from the Spanish cohort in CompLEEment-1 are consistent with previous data showing efficacy and a manageable safety profile of ribociclib plus letrozole as a first-line treatment option in a diverse group of patients with HR+, HER2– ABC. Acknowledgement: Dr. J. Gavilá-Gregori, Dr. M.J. Martinez-Serrano and Dr. M. Perelló contributed equally to this study.
NCT02941926.
Novartis Pharmaceuticals Corporation.
Novartis Pharmaceuticals Corporation.
E.M. Ciruelos: Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Pfizer. R. Villanueva Vázquez: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche. F. Moreno: Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy: MSD. I. Álvarez: Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. S. González-Santiago: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): AstraZeneca. A. Barnadas: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Genomic Health; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. B. Cantos: Research grant / Funding (institution), Study enrollment: Fundación para la Investigación del Hospital Puerta de Hierro de Majadahonda; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene; Advisory / Consultancy: AstraZeneca. M. Bellet Ezquerra: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly. M. Martín: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Taiho Oncology; Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Puma. N. Martínez: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.
Primordial Black Holes (PBHs) are gravitationally collapsed objects that may have been created by density fluctuations in the early universe and could have arbitrarily small masses down to the Planck ...scale. Hawking showed that due to quantum effects, a black hole has a temperature inversely proportional to its mass and will emit all species of fundamental particles thermally. PBHs with initial masses of ∼5.0×1014g should be expiring in the present epoch with bursts of high-energy particles, including gamma radiation in the GeV–TeV energy range. The Milagro high energy observatory, which operated from 2000 to 2008, is sensitive to the high end of the PBH evaporation gamma-ray spectrum. Due to its large field-of-view, more than 90% duty cycle and sensitivity up to 100TeV gamma rays, the Milagro observatory is well suited to perform a search for PBH bursts. Based on a search on the Milagro data, we report new PBH burst rate density upper limits over a range of PBH observation times. In addition, we report the sensitivity of the Milagro successor, the High Altitude Water Cherenkov (HAWC) observatory, to PBH evaporation events.
To determine pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after a single i.v. and i.m. administration of enrofloxacin and tissue residues after serial daily i.m. administration ...of enrofloxacin in pigs.
20 healthy male pigs.
8 pigs were used in a crossover design to investigate pharmacokinetics of enrofloxacin after a single i.v. and i.m. administration (2.5 mg/kg of body weight). Twelve pigs were used to study tissue residues; they were given daily doses of enrofloxacin (2.5 mg/kg, i.m. for 3 days). Plasma and tissue concentrations of enrofloxacin and ciprofloxacin were determined. Residues of enrofloxacin and ciprofloxacin were measured in fat, kidney, liver, and muscle.
Mean (+/-SD) elimination half-life and mean residence time of enrofloxacin in plasma were 9.64+/-1.49 and 12.77+/-2.15 hours, respectively, after i.v. administration and 12.06+/-0.68 and 17.15+/-1.04 hours, respectively, after i.m. administration. Half-life at alpha phase of enrofloxacin was 0.23+/-0.05 and 1.94+/-0.70 hours for i.v. and i.m. administration, respectively. Maximal plasma concentration was 1.17 +/-0.23 microg/ml, and interval from injection until maximum concentration was 1.81+/-0.23 hours. Renal and hepatic concentrations of enrofloxacin (0.012 to 0.017 microg/g) persisted for 10 days; however, at that time, ciprofloxacin residues were not detected in other tissues.
Enrofloxacin administered i.m. at a dosage of 2.5 mg/kg for 3 successive days, with a withdrawal time of 10 days, resulted in a sum of concentrations of enrofloxacin and ciprofloxacin that were less than the European Union maximal residue limit of 30 ng/g in edible tissues.
Hybrid polymeric networks composed of polyacrylamide and chitosan were developed to determine their swelling and ascorbic acid delivery kinetics at various chitosan concentrations. The hybrid ...acrylamide/chitosan hydrogels were synthesized in aqueous itaconic acid solution (1% w/w). Young’s modulus was also evaluated for the hydrogels, and the results were correlated with the swelling properties. Swelling experiments were carried out using three different pH solutions: acidic (pH 4 buffer solution), neutral (distilled water) and basic (pH 10 buffer solution). The results of the swelling study showed that the swelling properties of the network varied with the changes of the pH in the swelling solution, as well as concentration of chitosan. When chitosan concentration increased, the swelling capacity diminished, and therefore Young’s modulus increased. The results indicated that the swelling process followed a second order kinetics. The ascorbic acid diffusion inside the hydrogel follows a Fickian mechanism. The ascorbic acid diffusion coefficients are reported as a function of chitosan concentration.
Abstract only
Since 2010, members of the Puerto Rico Physiological Society at PHSU‐PRI have been involved in PhUn week, the annual K‐12 outreach program sponsored by The American Physiological ...Society. As part of the PhUn week 10th anniversary celebration, graduate students and staff from Ponce Health Sciences University ‐ Ponce Research Institute (PHSU‐PRI) took the “PhUn” to the elementary school students at Academia Santa María Reina in Ponce, Puerto Rico.
Aim
To assess the impact of a PhUn week activity in 3
rd
and 6
th
graders.
Methods
A team of graduate students, staff and faculty from PHSU‐PRI organized a half‐day workshop for a group of thirty‐eight 8–11 year old students and two science teachers. The workshop consisted of three short presentations (gastrointestinal system, circulatory system and nervous system) which included integrated videos, optical illusions, experiments and demonstrations. Next, the children were divided into smaller groups to rotate through five interactive stations featuring: histology, anatomy, emulsification, a life‐size neuron model and DNA extraction. At each station the PHSU‐PRI helpers explained what the purpose of the activity was and were available to answer questions. All activities were conducted in Spanish. Pre‐ and post‐tests evaluated student learning. Data was analyzed using an unpaired Student
t
‐test and chi‐square test.
Results
Students were clearly excited, demonstrated lots of enthusiasm, and were very proactive in all of the activities asking a lot of questions. A significant increase in the number of correct answers for all questions occurred following the workshop (gastrointestinal system p<0.001, circulatory system p<0.05 and nervous system p<0.001).
Conclusions
Short presentations and engagement of students from 3
rd
and 6
th
grade in interactive hands‐on activities in their native language helped to significantly increase their knowledge of basic physiological concepts.
Support or Funding Information
Supported in part by R25GM082406
The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal ...administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FBI-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed
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