Purpose: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. Methods: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m². Escalating dose levels of epirubicin were planned by increments of 5 mg/m² per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. Results: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m². Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. Conclusions: The recommended dose of epirubicin for phase II studies is 30 mg/m² in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.

In response to the challenges of urbanization, digitalization, and the e-commerce surge intensified by the COVID-19 pandemic, Smart Urban Logistics (SUL) has become a key framework for addressing last-mile delivery issues, congestion, and environmental impacts. This study introduces a System Dynamics (SD)-based approach to investigate how urban logistics and access management policies may interact. At the center, there is a Causal Loop Diagram (CLD) that illustrates dynamic interdependencies among fleet composition, access regulations, logistics productivity, and environmental externalities. The CLD is a conceptual basis for future stock-and-flow simulations to support data-driven decision-making. The approach highlights the importance of route optimization, dynamic access control, and smart parking management systems as strategic tools, increasingly enabled by Industry 4.0 technologies, such as IoT, big data analytics, AI, and cyber-physical systems, which support real-time monitoring and adaptive planning. In alignment with the Industry 5.0 paradigm, this technological integration is paired with social and environmental sustainability goals. The study also emphasizes public–private collaboration in designing access policies and promoting alternative fuel vehicle adoption, supported by specific incentives. These coordinated efforts contribute to achieving the objectives of the 2030 Agenda, fostering a cleaner, more efficient, and inclusive urban logistics ecosystem.

Different modes of transport are frequently used to transfer goods from origin to destination, especially on medium-long distances, in relation to the network supply, the available services, the costs. The transfer from one carrier to another, in an interchange node such as a port, a rail station, a logistics terminal, often implicates an increase of monetary and temporal costs, connected to material and immaterial operations. The principal aim is to minimize the overall cost of transport, but the freight interchange node can represent critical steps in logistics chain and for this reason much attention is now committed to actions to make efficient the functional organization of the terminal. In the last years an increasing interest is directed to the use of vehicles technologically advanced with automation of functions. The paper focuses on a particular technology, conceived recently, otherwise an intelligent rail wagon called AGW (Automated Guided Wagon) for handling of containers in a port. The use of intelligent system AGW as handling unit of containers in the yard, would allow the overcoming of diseconomies of scale and the reduction of the handling times and costs through a flexible management in relation to the characteristics of the transport supply and demand, the latter subject to a high variability. In the paper, after a brief description of the AGW technology and the advantages connected to the use of this handling system in a freight interchange node, the attention is focused on a comparative analysis between the handling system now operating in the container port (RTG, Straddle Carrier, AVG, etc.) and the system that involves the use of AGW. This analysis is made on the operational characteristics of the different handling systems, through the use of: functional schemes, with the aim to carry out evaluations related to the spatial, organizational and relational structure of container yard equipped with different handling unit; network models (graphical representation of links and paths; basic cost parameters) for the schematization and simulation of container handling in the yard; cost models for quantitative evaluation of monetary and temporal impacts, that derive from the use of different handling unit in the yard.

The remarkable demographic growth and economic development of the Southern and Eastern Mediterranean regions stimulate an ever increasing need for trade between the shores, especially from regions of North Africa and the Middle East towards Western European countries. Today, these exchanges take place mainly by sea and by roll on-roll off (Ro-Ro) ships; but the connections by container ships and by road transport are important too. Ro-Ro services are particularly crammed in some North-South directions, with relationships among few ports and with rather limited frequencies. Road transport, especially between the Middle East and Europe, has different limits in terms of cost, safety, and reliability. The paper proposes a hypothesis of a logistic organization on a Euro-Mediterranean scale, through the transition from a network of direct links to a hub and spoke (H&S) network, according to the scheme envisaged for air transport. The research aims to explore, within a framework of the socio-economic system and the mobility demand system, the feasibility of a H&S network for Ro-Ro freight in the Mediterranean basin, based on a hub with high logistical performances, limiting the planning to supply and process consequent impact assessments.

Freight fleet management (FM) can be defined as an optimization process of freight vehicles scheduling and routing, aimed at reducing time, costs, energy, and environmental impacts. In the specialized literature, there are many FM studies. The focus of this paper is on the FM in the context of a container port to increase the productivity and pursue the sustainability of the logistics node improving the performance by using freight advanced handling units (HUs). The use of automated HUs reduces the time and costs of each port activity, eliminating timewasters and increasing safety; however, it requires advanced intelligent management. Moreover, the automation is in line with energy and environmental sustainability. The paper aims to assess the impacts due to the automation of HUs by using a simulation approach. After a framework of traditional and automated HUs, allowing to highlight their main characteristics, the work considers the organizational problems of a container port and introduces a methodological approach to manage the FM of HUs. Finally, the application to a real context is presented to compare the present configuration of a container port with some project scenarios, considering different levels of automation, as the partial and total replacements of traditional HUs with advanced/automated vehicles.

The paper focuses on the receiving area of a logistics platform operating in the agri-food sector. The main aim of this work is to propose a “what to” approach for the resolution of problems related to the vehicles and goods receiving. The approach is based on a dynamic, stochastic, discrete-event micro-simulation model, which was properly specified and calibrated.The work proposes the formulation of the mathematical model defining the receiving activities in the logistics platform. The aim of the objective function is to minimize the average trucks turnaround in accordance with constraints allowing to establish the optimal entry sequence of the inbound trucks. The problem formulation considers the introduction of ITS to support the receiving activities management