Time trends for drug specific adverse events in patients on sunitinib; implications for remote monitoring.

INTRODUCTION: Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor used to treat metastatic renal cell carcinoma (mRCC). Patients on sunitinib do require regular in-person appointments to monitor for adverse events (AEs). Given the Covid-19 pandemic, regular in-person visits expose patients to an increased risk of infection in addition to potentially preventable travel costs. This study investigated the feasibility of implementing a remote monitoring strategy for patients being treated with sunitinib for mRCC by examining the time trends of AEs. MATERIALS AND METHODS: In this retrospective chart review of patients with a diagnosis of mRCC, 167 patients received sunitinib during their treatment. The time between initiation of treatment and the first AE was recorded. The AEs were categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5. Survival analysis was used to calculate the time-to-AE. RESULTS: Of the 167 patients identified, 145 experienced an AE (86.8%). Hypertension was the most common AE with 80% of AEs were ≤ Grade 2. Incidence of AE dropped by 91% after 3 months follow up and a further 36% after 6 months. The cumulative incidence of AEs were 87.8%, 94.6% and 98.0%, at 3, 6 and 9 months respectively. The severity of AEs observed were 39.3%, 38.6%, 20.7%, 1.4%,0% of Grade 1-5 events respectively. A trend of grade migration to less severe grades was also shown over time, with percentage of Grade ≥ 3 toxicity dropping from 22% between 0-3 months to 14% beyond 6 months follow up. CONCLUSIONS: The role of remote monitoring for mRCC patients on sunitinib remains relevant now with new waves of the Covid-19 pandemic, triggered by novel variants. The majority of AEs observed were of low severity ≤ Grade 2, with a trend of reduced AE frequency and severity most prevalent beyond 3 months of follow up. This data appears to support the implementation of a remote monitoring strategy 3 months after initiation of treatment.

A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study.

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.