ABSTRACT
Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.
Subject(s)
Dexamethasone/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Polymers/chemistry , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/chemistry , Antineoplastic Agents, Hormonal/pharmacokinetics , Child , Dexamethasone/chemistry , Dexamethasone/pharmacokinetics , Drug Liberation , Humans , Kaplan-Meier Estimate , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Treatment Outcome , Tumor Cells, Cultured , Young AdultABSTRACT
BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.
Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , COVID-19/epidemiology , Mammaplasty/statistics & numerical data , Neoadjuvant Therapy/statistics & numerical data , Adult , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , COVID-19/complications , Drug Therapy/statistics & numerical data , Female , Humans , Middle Aged , Neoadjuvant Therapy/adverse effects , Pandemics , Retrospective Studies , Treatment OutcomeSubject(s)
Abdominal Pain/etiology , Adrenal Gland Diseases/pathology , Castleman Disease/diagnosis , Edema/pathology , Fever/etiology , Abdominal Pain/diagnosis , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Azetidines/administration & dosage , Azetidines/therapeutic use , Bone Marrow/metabolism , Bone Marrow/pathology , Bortezomib/administration & dosage , Bortezomib/therapeutic use , Castleman Disease/drug therapy , Castleman Disease/pathology , Cyclosporine/administration & dosage , Cyclosporine/therapeutic use , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Drug Therapy, Combination , Fever/diagnosis , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Janus Kinase Inhibitors/administration & dosage , Janus Kinase Inhibitors/therapeutic use , Male , Middle Aged , Purines/administration & dosage , Purines/therapeutic use , Pyrazoles/administration & dosage , Pyrazoles/therapeutic use , Renal Insufficiency/etiology , Reticulin , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Thrombocytopenia/etiologyABSTRACT
BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.