Bisphosphonates Versus Denosumab for Prevention of Pathological Fracture in Advanced Cancers With Bone Metastasis: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Metastasis to the bone is one of the most common complications associated with advanced cancer. Patients with bone metastases are at risk of devastating skeletal related events, including pathological fractures. PURPOSE: The aim of this study was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject. METHODS: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures. RESULTS: Four RCTs (7,320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumor types were combined (odds ratio [OR] 0.86, 95% confidence interval [CI], 0.74 to 0.99, P = 0.04). Denosumab was favored, although not statistically significant, over ZA in endodermal origin (breast and prostate) (OR 0.85, 95% CI, 0.68 to 1.05, P = 0.13) and mesodermal origin tumors (solid tumors and multiple myeloma) (OR 0.87, 95% CI, 0.71 to 1.06, P = 0.16). DISCUSSION: Denosumab moderately reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases with statistical significance. When pathological fractures were grouped by tumor origin (endodermal or mesodermal), no statistical difference was observed between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens.

Zoledronic Acid Versus Denosumab for Prevention of Spinal Cord Compression in Advanced Cancers With Spine Metastasis: A Meta-Analysis of Randomized Controlled Trials.

STUDY DESIGN: Meta-analysis of randomized controlled trials (RCTs). OBJECTIVES: The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of spinal cord compression in patients with spine metastases from advanced cancers, by evaluating all available RCTs on this subject. METHODS: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of spinal cord compressions in spine metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were spinal cord compression. RESULTS: Three RCTs (5274 patients) were included. Denosumab was not significantly superior to ZA in reducing the likelihood of spinal cord compression, when all tumor types were combined (odds ratio [OR] 0.92, 95% confidence interval [CI; 0.66, 1.28], P = .66). Denosumab was not significantly favored over ZA in endodermal origin (breast and prostate; OR 0.72, 95% CI [0.43, 1.19], P = .20) and mesodermal origin tumors (solid tumors and multiple myeloma; OR 1.10, 95% CI [0.72, 1.69], P = .66). CONCLUSION: Denosumab does not significantly reduce the likelihood of spinal cord compressions in comparison to ZA in patients with spine metastases. When spinal cord compressions were grouped by tumor origin (endodermal or mesodermal), there remained no significant difference between denosumab and ZA. Further long-term studies are needed to determine the effectiveness of these treatment regimens.

Human Serum Albumin Nanoparticles for Use in Cancer Drug Delivery: Process Optimization and In Vitro Characterization.

Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ± 0.7 nm and 170.2 ± 1.4 nm with a surface charge of -5.6 ± 0.8 mV and -17.4 ± 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX), respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX-HSA-NPs, an in vitro drug release and cytotoxicity assay was performed on human breast cancer cell line (MCF-7). The PTX-HSA-NPs showed dose-dependent toxicity on cells of 52%, 39.3% and 22.6% with increasing concentrations of PTX at 8, 20.2 and 31.4 µg/mL, respectively. In summary, all parameters involved in HSA-NPs' preparation, its anticancer efficacy and scale-up are outlined in this research article.