Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide, mainly due to its high heterogeneity, resistance to therapy and late diagnosis, with a 5-year survival rate of less than 10%. This dismal prognosis has promoted strategies to develop more effective treatments. Nanoparticle-based strategies have emerged, in the last decades, as a great opportunity because they can enhance drug delivery and promote controlled release, presenting lower side effects than conventional therapeutic regimens. Moreover, nanoparticles can often be modified to target specific cells or to achieve a sustained release of the drugs into the tumor. However, very few nanoparticle-based therapies are clinically approved. Concretely for pancreatic cancer treatment only two nanoformulations have been approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) so far. Clinical translation of nanoparticles remains a challenge for modern medicine, and in particular for pancreatic cancer therapy, because of the complexity of the disease, and a lack of studies been performed in clinically relevant in vitro and in vivo models. In this review, we have summarized the most recent clinical trials using nanoparticle-based formulations in PDAC, giving a small context of the diverse types of nanoparticles employed and the most recent advancements in the field.

Cancer is still ranked among the top three causes of death in the 30- to 69-year-old age group in most countries and carries considerable societal and macroeconomic costs that differ depending on the cancer type, geography, and patient gender. Despite advances in several pharmacological approaches, the lack of stability and specificity, dose-related toxicity, and limited bioavailability of chemotherapy (standard therapy) pose major obstacles in cancer treatment, with multidrug resistance being a driving factor in chemotherapy failure. The past three decades have been the stage for intense research activity on the topic of nanomedicine, which has resulted in many nanotherapeutics with reduced toxicity, increased bioavailability, and improved pharmacokinetics and therapeutic efficacy employing smart drug delivery systems (SDDSs). Polymeric micelles (PMs) have become an auspicious DDS for medicinal compounds, being used to encapsulate hydrophobic drugs that also exhibit substantial toxicity. Through preclinical animal testing, PMs improved pharmacokinetic profiles and increased efficacy, resulting in a higher safety profile for therapeutic drugs. This review focuses on PMs that are already in clinical trials, traveling the pathways from preclinical to clinical studies until introduction to the market.

FOLFIRINOX and gemcitabine plus nab-paclitaxel (GN) are the most commonly used regimens in advanced pancreatic ductal adenocarcinomas (PDACs). As there is limited data on comparison of these two regimens, the present study was aimed to compare survivals and tolerance for both regimens through a match-pair analysis.

The data of 350 patients with metastatic and locally advanced PDAC, treated between January 2013 and December 2019, were retrieved. A 1:1 matching, using age and performance status, without replacement was performed by using nearest neighbour matching method.

A total of 260 patients (130 modified FOLFIRINOX and 130 GN) were matched. The median overall survival (OS) was 12.98 months [95% confidence interval (CI) 7.257-8.776 months] in modifications of FOLFIRINOX (mFOLFIRINOX) cohort and 12.06 months (95% CI 6.690-8.88 months) in GN group (P=0.080). The incidence of grade 3 and 4 infections, diarrhoea, oral mucositis, and fatigue was higher with mFOLFIRINOX. Patients who received second line therapy had improved OS as compared to those who did not (14.06 vs. 9.07 months, P<0.001).

GN and mFOLFIRINOX appear to have similar survival outcomes in an unselected match paired patient population with advanced PDAC. A markedly increased incidence of non-myelosuppressive grade 3 and grade 4 side-effects and lack of survival improvements suggest a need for nuanced use of the mFOLFIRINOX regimen. Administration of second-line chemotherapy improves OS in patients with advanced PDAC.