Assessment of the safety of glucocorticoid regimens in combination with abiraterone acetate for metastatic castration-resistant prostate cancer:a randomized, open-label phase 2 study

Importance: Abiraterone acetate is combined with prednisone, 5 mg, twice daily for metastatic castration-resistant prostate cancer (mCRPC) and with prednisone, 5 mg, once daily for newly diagnosed, high-risk, metastatic castration-sensitive prostate cancer. Understanding the physiological effects of these and other regimens is important. Objective: To evaluate the safety of abiraterone acetate with 4 glucocorticoid regimens. Design, Setting, and Participants: Open-label, randomized clinical trial (1:1:1:1) of 164 men with mCRPC from 22 hospitals in 5 countries who were randomly assigned to 1 of 4 intervention groups between June 2013 and October 2014. Analyses were conducted from August 2017 to June 2018. Interventions: Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily (n = 41), 5 mg once daily (n = 41), 2.5 mg twice daily (n = 40), or dexamethasone, 0.5 mg, once daily (n = 42). Main Outcomes and Measures: Primary end point was no mineralocorticoid excess (grade ≥1 hypokalemia or grade ≥2 hypertension) through 24 weeks (6 cycles) from treatment. Results: Of 164 men (median [range] age, 70 [50-90] years) randomized to receive abiraterone acetate, 1000 mg, daily with prednisone, 5 mg, twice daily, once daily, or 2.5 mg twice daily, or dexamethasone, 0.5 mg, once daily, 24 (70.6%) of 34 patients (95% CI, 53.8%-83.2%), 14 (36.8%) of 38 patients (95% CI, 23.4%-52.7%), 21 (60.0%) of 35 patients (95% CI, 43.6%-74.4%), and 26 (70.3%) of 37 patients (95% CI, 54.2%-82.5%), respectively, had no mineralocorticoid excess. Plasma adrenocorticotrophic hormone and urinary mineralocorticoid metabolites after 8 weeks were higher with prednisone, 2.5 mg, twice daily and 5 mg once daily than with 5 mg twice daily or dexamethasone, 0.5 mg, once daily. The level of urinary glucocorticoid metabolites appeared higher in patients who did not meet the primary end point, regardless of glucocorticoid regimen. Total lean body mass decreased in the prednisone groups and total body fat increased in the prednisone, 5 mg, twice daily and dexamethasone groups. In the dexamethasone group, there was an increase in serum insulin and homeostatic model assessment of insulin resistance, while total bone mineral density decreased. In the prednisone, 5 mg, twice daily, 5 mg once daily, 2.5 mg twice daily, and dexamethasone groups, median radiographic progression-free survival was 18.5, 15.3, 12.8, and 26.6 months, respectively. Conclusions and Relevance: Abiraterone acetate with prednisone, 5 mg, twice daily or dexamethasone, 0.5 mg, once daily met the prespecified threshold for the primary end point (95% CI excluded 50% mineralocorticoid excess); abiraterone acetate with prednisone, 5 mg, once daily or 2.5 mg twice daily did not meet the threshold. Abiraterone acetate in combination with dexamethasone appeared to be particularly active but may be associated with adverse metabolic consequences

Mise en oeuvre de carottages de sol et de minirhizotrons pour l'étude à long terme de la réponse des fines racines d'épicéa (Picea abies (L.) Karst.) à l'augmentation de la concentration en CO2 dans l'atmosphère et la nutrition minérale

Use of soil cores and minirhizotrons for the long-term study of the response of Norway spruce fine roots (Picea abies (L.) Karst.) to the increase in CO2 concentration in the atmosphere and nutrition. The fine root biomass of Norway spruce (Picea abies (L.) Karst.) grown in open top chambers (OTCs) under elevated CO2 since 1987 was investigated with soil cores and minirhizotrons, at Vielsalm (Ardenne, Belgium). Four levels of CO2 concentration (700, 580, 470 and 350 µmol.mol-1 CO2) were applied in combination with two nutrition regimes: the optimal nutrition and the nutrition corresponding to the local brown forest soil. First soil coring was performed in 1997 to describe the root biomass and root distribution according depth, at the initial stage of this study. Soil coring was repeated in 2003. Two observation and measurement campaigns using minirhizotrons were carried out in 2001 and in 2002. These latter measurements shown a very large proportion of very fine roots within the root classes classically reported in the literature: ]0-1 mm], ]1-2 mm], ]2-5 mm] and > 5 mm. Among the 2252 roots we regularly observed in minirhizotrons, more than 90 % were thinner than 0.5 mm in diameter, less than 2 % were in the range [1-3 mm[ in diameter and their mean was 0.28 mm. Calculations on the 42 Biotechnol. Agron. Soc. Environ. 2004 8 (1), 41-53 Lebègue C., Laita É., Perrin D., Pissart G. roots observed with minirhizotrons shown that root biomass under elevated atmospheric CO2 concentrations (580 and 700 µmol.mol-1 CO2) were two times higher than root biomass under ambient concentration (350 µmol.mol-1 CO2). As these figures are based on specific root length (SRL), they are supposed to be largely underestimated. A larger proportion of these roots were exploring the upper soil horizons under elevated CO2. Norway spruce showed an annual production cycle of fine roots, independent from the atmospheric CO2 concentration. Increased CO2 affected root branching. Under elevated CO2 roots were shorter and four times more branched than roots under ambient CO2. These differences were not to be observed for thicker root (> 0.5 mm diameter) using soil cores. The optimum nutrition regime conducted in this experiment induced, in comparison to the 'normal'nutrition regime, a root system made off smaller but branchier roots mostly located in the upper layers, independently from the CO2 atmospheric concentration

EFOBEL un modèle de calcul de la séquestration du carbone par les forêts, selon les termes des Accords de Marrakech et les engagements de rapportage de la Belgique au Protocole de Kyoto

EFOBELa computing model of carbon sequestration in forests, as established in the Marrakech Agreements and Belgium's reporting commitment to the Kyoto Protocol. This article synthesizes the numerous corollaries under the definitions of "forest" and "forest management", which result from the good practice guidance for land use, land-use change and forestry, as established by the Marrakech Agreements and the Kyoto Protocol reporting needs. This guide complements the greenhouse gases inventory reference manual as scientific support for the United Nations Framework Convention on Climatic Change (UNFCCC). Belgium committed herself to the highest level of reporting as Party to Annex 1 of the UNFCCC and a signatory to the Kyoto Protocol. This article lists the forestry data needed for the reporting and proposes an algorithm, which articulates them and models the C-stock evolution in the forest ecosystems of Belgium

Abiraterone acetate plus prednisone for the Management of Metastatic Castration-Resistant Prostate Cancer (mCRPC) without prior use of chemotherapy : report from a large, international, real-world retrospective cohort study

Background: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated. Methods: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment. Results: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0–81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2–133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2–11.1) and the median PFS was 10.8 months (95%CI: 9.6–11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001). Conclusions: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population