Nutritional Support With Oral Polymeric Formulation Enriched With Transforming Growth Factor beta 2 (TGF-β2) in Allogenic Hematopoietic Stem Cells Transplantation (Allo-hsct): A Prospective Interventional Study

PurposeIn the allogeneic transplant setting (allo-HSCT), the prevalence of malnutrition at admission is usually low, but at discharge, may be 60% or more and it may affect the transplant outcome.The aim of this study was to reduce the incidence of severe malnutrition (PG-SGA C) at day + 28 days from allo-HSCT in patients supported with an oral polymeric formulation enriched with Transforming Growth Factor beta 2 (TGF-β2).MethodsFifty-one patients were consecutively enrolled between March 2020 and June 2021 in this prospective interventional study. As a group of control, we have retrospectively analyzed an observational cohort composed by thirty patients submitted to allo-HSCT from august 2017 and august 2018 in our institution.ResultsThe incidence of severe malnourished patients (PG-SGA C) at + 28 days was significantly lower in the group with an oral nutritional support (ONS) treatment ratio (TR) major than 50% (TR>50%) in comparison to the ones with less than 50% ONS assumption (TR<50%) (13% vs 88.9% P=0.000). Interestingly, cumulative incidence of gastrointestinal (GI) aGVHD was significantly lower in patients assuming 50% or more of the prescribed ONS dose in comparison to those who assumed less than 50% of ONS (0%, vs 29.6%; p=0.005). Pneumonia was more frequent in patients with TR < 50% compared to patients with TR > 50% (48.1 % and 12.5 % respectively)(p=0.006).ConclusionMODULEN-IBD® seems to be a promising ONS to reduce malnutrition in allogeneic stem cell transplantation and should be tested in a randomized controlled prospective trial. MODULEN-IBD® may also have some positive immunological effects on gastrointestinal GVHD and infections that should be explored in larger studies.

Preliminary in vitro Evaluation of a Semisynthetic Oestrogen Polymer-based Formulation

Oestrogen hormones play key roles in the human body, are involved in complex mechanisms, both beneficial and unwanted. Because semisynthetic oestrogens are commonly used today in various hormonal therapies, they has inevitably been linked to the appearance of certain carcinogenic processes, which are primarily based on oestrogen-based drugs, either as initiators or promoters. A promising alternative that can help reduce unwanted effects is to capture the active substance in a polymeric matrix that is capable of retaining its biological activity. In this study, activity on the viability of breast cancer cells with expressed oestrogen receptors of a polymeric formulation with ethinylestradiol and polylactic acid was evaluated.

Phase III study of sustained release granisetron (APF530) compared to palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV)

9627 Background: APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days. Two doses (5 and 10 mg) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron. Efficacy was evaluated in acute (0–24 hrs) and delayed (24–120 hrs) CINV among patients receiving moderate (MEC) or highly (HEC) emetogenic chemotherapy. Methods: Randomized, blinded patients (n=1,395) were stratified into MEC or HEC according to Hesketh et al 1999, and assigned to receive either dose of APF530 or palonosetron. Dexamethasone use was standardized based on the emetogenic strata. Patient diaries recorded emetic episodes, nausea and rescue medications over a 5-day period. Primary endpoint was Complete Response (CR), defined as no emetic episodes and no rescue medication. Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15%. Results: APF530 was well tolerated. Adverse events were consistent with those previously reported for granisetron. For APF530 Tmax was observed about 24 hrs with sustained levels over 120 hrs. For MEC acute phase CR rates of 74.8% (n=214), 76.9% (n=212) and 75.0% (n=208) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 51.4%, 59.0% and 57.7% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. For HEC acute phase CR rates of 77.7% (n=229), 81.3% (n=240) and 80.7% (n=238) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 64.6%, 68.3% and 66.4% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Efficacy was maintained with APF530 over multiple cycles (up to 4). Conclusions: Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC. Only the higher dose of APF530 (10 mg granisetron) was non-inferior to palonosetron during the delayed phase of MEC. Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC. [Table: see text]