TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m 2, oxaliplatin 85 mg/m 2, L-leucovorin 200 mg/m 2, 5-fluoruracil 2400 mg/m 2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722

Implementation of novel technologies to reduce the environmental spread of pesticides in water and soil using natural mineral carriers and agri-food waste soil amendments

L'abstract è presente nell'allegato / the abstract is in the attachmen

Alginate Nanohydrogels as a Biocompatible Platform for the Controlled Release of a Hydrophilic Herbicide

The large-scale application of volatile and highly water-soluble pesticides to guarantee crop production can often have negative impacts on the environment. The main loss pathways are vapor drift, direct volatilization, or leaching of the active substances. Consequently, the pesticide can either accumulate and/or undergo physicochemical transformations in the soil. In this scenario, we synthesized alginate nanoparticles using an inverse miniemulsion template in sunflower oil and successfully used them to encapsulate a hydrophilic herbicide, i.e., dicamba. The formulation and process conditions were adjusted to obtain a unimodal size distribution of nanohydrogels of about 20 nm. The loading of the nanoparticles with dicamba did not affect the nanohydrogel size nor the particle stability. The release of dicamba from the nanohydrogels was also tested: the alginate nanoparticles promoted the sustained and prolonged release of dicamba over ten days, demonstrating the potential of our preparation method to be employed for field application. The encapsulation of hydrophilic compounds inside our alginate nanoparticles could enable a more efficient use of pesticides, minimizing losses and thus environmental spreading. The use of biocompatible materials (alginate, sunflower oil) also guarantees the absence of toxic additives in the formulation

Alginate Nanohydrogels as a Biocompatible Platform for the Controlled Release of a Hydrophilic Herbicide

The large-scale application of volatile and highly water-soluble pesticides to guarantee crop production can often have negative impacts on the environment. The main loss pathways are vapor drift, direct volatilization, or leaching of the active substances. Consequently, the pesticide can either accumulate and/or undergo physicochemical transformations in the soil. In this scenario, we synthesized alginate nanoparticles using an inverse miniemulsion template in sunflower oil and successfully used them to encapsulate a hydrophilic herbicide, i.e., dicamba. The formulation and process conditions were adjusted to obtain a unimodal size distribution of nanohydrogels of about 20 nm. The loading of the nanoparticles with dicamba did not affect the nanohydrogel size nor the particle stability. The release of dicamba from the nanohydrogels was also tested: the alginate nanoparticles promoted the sustained and prolonged release of dicamba over ten days, demonstrating the potential of our preparation method to be employed for field application. The encapsulation of hydrophilic compounds inside our alginate nanoparticles could enable a more efficient use of pesticides, minimizing losses and thus environmental spreading. The use of biocompatible materials (alginate, sunflower oil) also guarantees the absence of toxic additives in the formulation.</jats:p

Dispersione ambientale di prodotti fitosanitari: confronto tra formulazioni tradizionali e nano-supportate

L’uso di pesticidi in agricoltura presenta numerosi vantaggi ma anche problematiche ambientali. L’uso incontrollato ed eccessivo di fitofarmaci ha portato negli anni alla contaminazione delle matrici ambientali. Per risolvere questi problemi è stata recentemente sviluppata una nano-formulazione ecocompatibile a base Dicamba, un erbicida per le infestanti a foglia larga, realizzata con materiali reperibili sul mercato a basso costo. Nel presente lavoro sono riportate le metodologie e i risultati di alcuni test di laboratorio condotti per determinare la riduzione della mobilità in aria, acqua e suolo. In particolare sono stati svolti test di volatilizzazione e prove di trasporto in condizioni sature ed insature. I risultati di queste ultime due tipologie di prove sono stati interpretati mediante software numerici quali MNMs e Hydrus1D ed utilizzati come dati di partenza per una modellazione del trasporto dell’erbicida e della nano-formulazione in 3D. Gli stessi risultati sono serviti per implementare un’analisi di rischio sanitario-ambientale con il software Risk-net e per porre le basi per un futuro studio di LCA (Life Cycle Assessment)

A novel nano-formulation to reduce the environmental dispersion of herbicides

&amp;lt;p&amp;gt;The use of pesticides in agriculture has numerous advantages but also significant environmental drawbacks; The uncontrolled or excessive use of agrochemicals has progressively contributed to the contamination of environmental matrices, and in particular of soils and groundwater. To contribute solving these issues, an eco-compatible nano-formulation was recently developed by the authors to help controlling the environmental dispersion of Dicamba, a herbicide widely used to control broadleaf weeds; Dicamba is highly soluble and moderately volatile, but is less toxic and persistent compared to other competing herbicides. The proposed nano-formulation was developed using eco-compatible, low-cost materials, including natural clays an biopolymers, with the aim to reduce Dicamba volatilization (thus reducing dispersion in air, and consequently potential impacts on both workers and neighboring crops) and solubility (thus reducing infiltration during and after application, and consequently uncontrolled dispersion in the subsoil). &amp;amp;#160;In this work, the results of laboratory and greenhouse tests are discussed, comparing the efficacy of the nano-formulation against the pure herbicide compound and a commercial Dicamba-based product, in terms of volatilization, mobility in porous media (both saturated and unsaturated) and efficacy in weed control. The column tests results are modeled using colloid transport software (namely MNMs and Hydrus) and used for the development of a preliminary field-scale model of herbicide application and dispersion in the subsoil. The work was developed in the framework of the project Nanograss, co-funded by Compagnia di San Paolo Foundation.&amp;lt;/p&amp;gt; </jats:p