Phase Ib Trial of Phenformin in Patients with V600-mutated Melanoma Receiving Dabrafenib and Trametinib.

Purpose: Preclinical studies show that activation of AMP kinase by phenformin can augment the cytotoxic effect and RAF inhibitors in BRAF V600-mutated melanoma. We conducted a phase Ib dose-escalation trial of phenformin with standard dose dabrafenib/trametinib in patients with metastatic BRAF V600-mutated melanoma.

Experimental Design: We used a 3+3 dose-escalation design which explored phenformin doses between 50 and 200 mg twice daily.

Developing guidance for feeding tube administration of oral medications.

Background: Drug administration through feeding tubes presents many challenges to the healthcare provider. There is little information available on medications than can be delivered safely when crushed and what efforts can be implemented to minimize clogging the feeding tube. Our institution requested a comprehensive examination of all oral medications for the feeding tube route.

Keratinocytes coordinate inflammatory responses and regulate development of secondary lymphedema.

Epidermal changes are histological hallmarks of secondary lymphedema, but it is unknown if keratinocytes contribute to its pathophysiology. Using clinical lymphedema specimens and mouse models, we show that keratinocytes play a primary role in lymphedema development by producing T-helper 2 (Th2) -inducing cytokines. Specifically, we find that keratinocyte proliferation and expression of protease-activated receptor 2 (PAR2) are early responses following lymphatic injury and regulate the expression of Th2-inducing cytokines, migration of Langerhans cells, and skin infiltration of Th2-differentiated T cells.

A prospective study of dysgeusia and related symptoms in patients with multiple myeloma after autologous hematopoietic cell transplantation.

Background: Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its associations with symptom burden, nutrition, chemotherapy pharmacokinetics (PK), and the oral microbiome.

Methods: We conducted a single-center, prospective feasibility study (NCT03276481) of patients with multiple myeloma undergoing auto-HCT.

TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.

Background: Secondary lymphedema is a common complication of cancer treatment, and previous studies have shown that the expression of transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic and anti-lymphangiogenic growth factor, is increased in this disease. Inhibition of TGF-β1 decreases the severity of the disease in mouse models; however, the mechanisms that regulate this improvement remain unknown.

Methods: Expression of TGF-β1 and extracellular matrix molecules (ECM) was assessed in biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL).

Intratumoral Injection of -NT Spores in Patients with Treatment-refractory Advanced Solid Tumors.

Purpose: Intratumorally injected -NT (nontoxic; lacking the alpha toxin), an attenuated strain of , replicates within hypoxic tumor regions resulting in tumor-confined cell lysis and inflammatory response in animals, which warrants clinical investigation.

Patients And Methods: This first-in-human study (NCT01924689) enrolled patients with injectable, treatment-refractory solid tumors to receive a single intratumoral injection of -NT across 6 dose cohorts (1 × 10 to 3 × 10 spores, 3+3 dose-escalation design) to determine dose-limiting toxicities (DLT), and the maximum tolerated dose.

Results: Among 24 patients, a single intratumoral injection of -NT led to bacterial spores germination and the resultant lysis of injected tumor masses in 10 patients (42%) across all doses.

ASPEN Safe Practices for Enteral Nutrition Therapy [Formula: see text].

Enteral nutrition (EN) is a valuable clinical intervention for patients of all ages in a variety of care settings. Along with its many outcome benefits come the potential for adverse effects. These safety issues are the result of clinical complications and of process-related errors.

Quality Control Analytical Methods: Method Validation.

To properly determine the accuracy of a pharmaceutical product or compounded preparation, tests must be designed specifically for that evaluation. The procedures selected must be verified through a process referred to as method validation, an integral part of any good analytical practice. The results from a method validation procedure can be used to judge the quality, reliability, and consistency of analytical results.

PFAT5 and the Evolution of Lipid Admixture Stability.

PFAT5 is defined by United States Pharmacopeia Chapter 729 as follows: the "percentage of fat residing in globules larger than 5 µm (PFAT5) for a given lipid injectable emulsion [is] not to exceed 0.05%." The unstable aggregates are trapped in lungs, liver, and the reticuloendothelial system.

Osmolality, pH, and compatibility of selected oral liquid medications with an enteral nutrition product.

When selecting medication for feeding tube administration, the liquid formulation is selected, so as to avoid obstructions that may occur from incompletely crushing a solid dosage form. Liquid medications can present issues of intolerance and compatibility when administered via a feeding tube. A predictor of intolerance is the liquid's osmolarity, and a predicator of compatibility is the liquid's pH value.

ARN-509: a novel antiandrogen for prostate cancer treatment.

Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration-resistant prostate cancer (CRPC), the most advanced form of this disease. While established and novel AR pathway-targeting agents display clinical efficacy in metastatic CRPC, dose-limiting side effects remain problematic for all current agents. In this study, we report the discovery and development of ARN-509, a competitive AR inhibitor that is fully antagonistic to AR overexpression, a common and important feature of CRPC.

Recommendations for compounding medications for feeding tube administration.

There are no commercially available liquid medications that are formulated for feeding tube administration. The goal and indication of orally administered medications formulated in liquids is for pediatric patients or patients with limited ability to swallow tablets. Pharmacists who are considering compounding medications for feeding tube administration must be aware of the many issues involved in preparing drugs for this purpose.

Warfarin bioavailability with feeding tubes and enteral formula.

Background: Earlier literature showed reduced efficacy of warfarin when co-administered with enteral nutrition formulas through feeding tubes. This study used an in vitro model for gastric administration of warfarin through a feeding tube to evaluate potential causes for reduced warfarin absorption when administered through feeding tubes.

Methods: There were 2 phases of the study.

Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously.

Purpose: To evaluate the safety, pharmacokinetics, and biological activity of suberoylanilide hydroxamic acid (SAHA) administered by 2-h i.v. infusion in patients with advanced cancer.