99 research outputs found
Effects of cabozantinib on bone turnover markers in real-world metastatic renal cell carcinoma
No full textBackground: Cabozantinib strongly inhibits osteoclast differentiation and bone resorption in vitro. We aimed to evaluate its effect on bone turnover markers (BTMs) in metastatic renal cell carcinoma. Methods: This is a monocentric prospective study on patients with mRCC treated with cabozantinib between October 2016 and July 2018. We collected blood samples at baseline and after 3 and 6 months of treatment. We compared sets of data obtained from plasma samples in the whole population with unpaired 2-tailed Student t tests and data for a subset of patients for which all timepoints were available with paired 2-tailed Student t tests. We used the Kaplan-Meier method for survival analyses and the log-rank test to compare the curves. Results: Our analysis included 39 patients. At month 3, the mean C-terminal cross-linked telopeptides of type I collagen (CTx) and the mean N-terminal propeptide of type 1 collagen (PINP) levels were significantly decreased in the whole population (p = 0.013 and p < 0.0001, respectively), as well as at paired analysis (p = 0.015 and p = 0.045, respectively). No differences were observed between baseline and 6 months (p = 0.053 and p = 0.087, respectively). After 3 months, the mean parathyroid hormone (PTH) levels significantly increased in the whole population (p = 0.004), as well as at paired analysis; the mean PTH levels increased significantly at 3 and 6 months, respectively (p = 0.019 and p = 0.041, respectively). Changes in BTM levels were not associated with outcome. Conclusions: Cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx and showed a transient secondary increase of PTH
Effects of cabozantinib on bone turnover markers in real-world metastatic renal cell carcinoma
No full textBackground: Cabozantinib strongly inhibits osteoclast differentiation and bone resorption in vitro. We aimed to evaluate its effect on bone turnover markers (BTMs) in metastatic renal cell carcinoma. Methods: This is a monocentric prospective study on patients with mRCC treated with cabozantinib between October 2016 and July 2018. We collected blood samples at baseline and after 3 and 6 months of treatment. We compared sets of data obtained from plasma samples in the whole population with unpaired 2-tailed Student t tests and data for a subset of patients for which all timepoints were available with paired 2-tailed Student t tests. We used the Kaplan-Meier method for survival analyses and the log-rank test to compare the curves. Results: Our analysis included 39 patients. At month 3, the mean C-terminal cross-linked telopeptides of type I collagen (CTx) and the mean N-terminal propeptide of type 1 collagen (PINP) levels were significantly decreased in the whole population (p = 0.013 and p < 0.0001, respectively), as well as at paired analysis (p = 0.015 and p = 0.045, respectively). No differences were observed between baseline and 6 months (p = 0.053 and p = 0.087, respectively). After 3 months, the mean parathyroid hormone (PTH) levels significantly increased in the whole population (p = 0.004), as well as at paired analysis; the mean PTH levels increased significantly at 3 and 6 months, respectively (p = 0.019 and p = 0.041, respectively). Changes in BTM levels were not associated with outcome. Conclusions: Cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx and showed a transient secondary increase of PTH
Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis
No full textBackground: In recent years, new therapeutic combinations based on immunotherapy provided significant benefits as a first-line treatment for patients with advanced renal cell carcinoma (mRCC). Objective: This work aims to address the lack of head-to-head comparisons and the uncertainty of the benefit from immunotherapy-based combinations in all the International Metastatic RCC Database Consortium (IMDC) subgroups. Design, setting, and participants: A systematic review and a network meta-analysis were performed. Overall survival (OS) in the intention-to-treat (ITT) population was the primary endpoint. OS according to IMDC subgroups (favorable, intermediate, poor), PD-L1 expression, and grade ⩾3 adverse events (AEs) were secondary endpoints. A SUCRA analysis was performed. Results and limitations: Six randomized phase III trials with 5121 patients were included. There was a high likelihood (82%) that nivolumab-cabozantinib was the preferred treatment in OS. The benefit of ICI-based combinations over sunitinib was unclear in the favorable-risk subgroup. Nivolumab-ipilimumab had the best risk/benefit ratio among all the ICI-based combinations. The limitations were the lack of individual patient data; the heterogeneity of patients’ characteristics, trial designs, and follow-up times; and a limited number of studies for indirect comparisons. Conclusions: A customized approach for the first-line treatment of patients with mRCC should consider the risk/benefit profile of each treatment option, especially considering the likeliness of long-term survival finally reached in this setting
Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study
No full textBackground
Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum–taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS).
Methods
We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007–2016 with the combination of carboplatin AUC 2 plus paclitaxel 80 mg/m2, both given on days 1 and 8 in every 21-day cycle.
Results
264 patients were evaluable for treatment safety and activity. The objective response rate (ORR) was 44.7%. Median PFS and OS were 8.6 and 23.7 months, respectively. Triple-negative breast cancer (TNBC) patients had significantly lower PFS and OS times compared to other biology groups. At multivariable analysis, previous exposure to taxanes, HR-positive HER2-negative biology, a higher number of metastatic sites, and de novo metastatic disease at diagnosis were associated with reduced PFS, while receiving maintenance therapy correlated with improved PFS. Overall, the treatment was quite well tolerated, with 10.2% of patients discontinuing one or both drugs because of adverse events (AEs). G3–G4 neutropenia occurred in 16.8% of patients, while the incidence of febrile neutropenia was 2.3%.
Conclusions
Weekly carboplatin–paclitaxel regimen is active and well tolerated in mBC treatment. Prospective studies should be conducted to compare its efficacy and tolerability with standard single-agent paclitaxel or docetaxel treatment schedules, as well as with more recent combination regimens
Modelling of monoliths for adsorption processes
No full textStraight-channel monoliths are a promising means to achieve process intensification of adsorption processes compared to conventional packed beds. Their main benefits are handling of high throughputs and good thermal management. The efficiency of a straight-channel monolith can be assessed via the definition of its height equivalent to a theoretical plate (HETP) and pressure drop. This thesis aims at developing a systematic procedure for the derivation of HETP correlations for industrially relevant straight-channel monoliths and review the pressure drop correlations for monoliths available in the literature. The HETP correlations derived are validated against full 3D numerical simulations of the single representative channel of each straight-channel monolith under analysis. The HETP correlations predict with great accuracy the HETP from numerical simulations. Moreover, simplified reduced order models are developed. The models are able to capture the overall dynamics of the 3D simulations for both isothermal and linear conditions, and non-isothermal and non-linear ones. The reduced order models are fully predictive, and strongly rely on accurate equilibrium and kinetic parameters. Given the relevance of reliable equilibrium and kinetic parameters for the simulation of monoliths, this thesis further investigates how to model multicomponent adsorption on heterogeneous solids, and how to extract kinetic parameters from experiments.
The second part of this work presents the multisite rigid adsorbent lattice fluid (multi-RALF) model, a novel thermodynamic theory to model multicomponent adsorption on heterogeneous adsorbents. The parameterisation of multi-RALF is analysed in regard to the azeotropic adsorption of benzene and propene on silicalite and to the adsorption of CO2 on the flexible synthetic zeolite (Na,TEA)-ZSM-25. The former study is carried out using molecular simulations, while the latter uses experimental data. The results of the molecular simulations show that the azeotrope is caused by steric hindrance of benzene in the adsorbent framework. Once correctly parametrised using single component isotherms, multi-RALF can predict the azeotrope of the system. Multi-RALF has been proven to be an effective model for the flexibility of (Na,TEA)-ZSM-25 upon CO2 adsorption, as well. Experimental isotherms of CO2 adsorption on (Na,TEA)-ZSM-25 always present an inflection at a constant adsorbed amount. This has been explained as a gate opening effect. The adsorbent is made of two sites, α and β. The site β becomes accessible only after a critical uptake of 0.6 mol/kg. At this uptake, the cations blocking the site β interact with the adsorbate and move away from the windows of the β site. This effect leads to the inflection in the isotherm and a relaxation of the solid framework with a small breathing effect. The breathing behaviour effect on the system kinetics is then investigated using the zero length column (ZLC) technique. The ZLC curves at different flowrates and temperatures always present a transition between an equilibrium controlled regime at high partial pressures of CO2, while becoming kinetically controlled in the limit of zero-loading. The transition between the two regimes is related to the cation movement, and it is carefully accounted for in a ZLC numerical model which successfully fits the experimental data.
Finally, thermal frequency response (TFR) measurements for air separation on the zeolite LiLSX are presented. This is a fast diffusing system, difficult to study with commercial equipment. Hence, the purpose-built dual piston pressure swing adsorption apparatus is used for the experiments. Two models are developed to analyse both single- and multi-component measurements. From the single component model, a tortuosity of 3.3 is regressed, while the multicomponent data show a N2/O2 selectivity of 6. Both values are in accordance with the available literature. TFR has proven to be a powerful technique to handle challenging diffusing systems, able to effectively discriminate the relevant mass and heat transfer time constants as shown from experiments at conditions relevant to process application. The work here presented aimed at providing a reliable methodology for modelling of monoliths and derivation of the relevant equilibrium and kinetic parameters. In future, the combination of the monoliths’ models and multi-RALF could become a robust and reliable tool for the deployment of monoliths for process intensification
The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera.
No full textComments on “Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476)
No full textsj-docx-1-tau-10.1177_17562872211053189 – Supplemental material for Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis
No full textSupplemental material, sj-docx-1-tau-10.1177_17562872211053189 for Is there a preferred first-line therapy for metastatic renal cell carcinoma? A network meta-analysis by Carlo Cattrini, Carlo Messina, Chiara Airoldi, Sebastiano Buti, Giandomenico Roviello, Alessia Mennitto, Orazio Caffo, Alessandra Gennari and Melissa Bersanelli in Therapeutic Advances in Urology</p
Current adjuvants and new perspectives in vaccine formulation
No full textGiven the important role of adjuvants in prophylactic vaccines, identification and development of new adjuvants with enhanced efficacy and safety is necessary. The use of adjuvants with immunopotentiating properties that can direct the immune responses to humoral or cell-mediated immunity and can induce T-cell responses has made it possible to design more protective vaccines. Although current regulations focus on traditional adjuvants, notably aluminum and calcium salts, advances have been made in regulatory considerations. The regulatory agencies for the evaluation of medicinal products are actively drafting guidance on requirements for the evaluation of new adjuvants. This article briefly summarizes the most widely studied adjuvants in vaccination, including those licensed for human vaccines and the regulatory aspects relevant to adjuvant quality at development stages
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