Fosaprepitant dimeglumine for the management of chemotherapy-induced nausea and vomiting: patient selection and perspectives

Candelario, Nellowe; Lu, Marvin

doi:10.2147/cmar.s93620

Cited by 10 publications

(13 citation statements)

References 30 publications

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“…It aids in prevention of both delayed and acute nausea and vomiting associated with cancer chemotherapy 24 . Fosaprepitant is a neurokinin 1 receptor (NK-1R) antagonist that binds and deactivate NK-1R leading to downstream effect such as Ca 2+ signaling through the g-protein coupled receptor (GPCR) cascade, which in turn leads to cellular sequestration resulting in vomiting [24][25][26] . Fosaprepitant exerts its effect on targeted cells by passing across the blood brain barrier (BBB) to its target destination 23 .…”

Section: Discussionmentioning

confidence: 99%

Structural insights of human N-acetyltransferase 10 and identification of its potential novel inhibitors

Dalhat

Altayb

Khan

et al. 2021

Sci Rep

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N-acetyltransferase 10 (NAT10), is an acetyltransferase that regulates RNA stability and translation processes. Association of NAT10 with several diseases including cancer, makes it a promising therapeutic target. Remodelin is the only known NAT10 inhibitor, but the structural information related to its binding with NAT10 is still obscure. Here, we predicted the human NAT10 structure using homology modeling that was not available previously and used human NAT10 to identify the novel binding site(s) of Remodelin. The alignment of the modeled human NAT10 showed 24% identity and 37% positivity with crystal structure of tRNA (Met) cytidine acetyltransferase. Molecular docking showed binding of Remodelin with NAT10 in acetyl-CoA binding pocket. Additionally, we screened a library of FDA-approved drugs for the identification of novel inhibitors of NAT10 activity. Binding score showed that four drugs namely, Fosaprepitant (− 11.709), Leucal (− 10.46), Fludarabine (− 10.347) and Dantrolene (− 9.875) bind to NAT10 and have better binding capability when compared with Acetyl-CoA (− 5.691) and Remodelin (− 5.3). Acetyl-CoA, Remodelin, and others exhibit hits for hydrophobic, hydrophilic and hydrogen interactions. Interestingly, Remodelin and others interact with the amino acid residues ILE629, GLY639, GLY641, LEU719, and PHE722 in the Acetyl-CoA binding pocket of NAT10 similar to Acetyl-CoA. Our findings revealed that Fosaprepitant, Leucal, Fludarabine, and Dantrolene are promising molecules that can be tested and developed as potential inhibitors of NAT10 acetyltransferase activity.

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Section: Discussionmentioning

confidence: 99%

Structural insights of human N-acetyltransferase 10 and identification of its potential novel inhibitors

Dalhat

Altayb

Khan

et al. 2021

Sci Rep

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“…[1][2][3][4] Among the NK 1 RAs, injectable fosaprepitant (FosAPR) is widely used but has been reported to be associated with an increased risk/incidence of injection site reactions (ISRs), particularly in patients receiving anthracycline-based chemotherapy regimens, necessitating FosAPR dosing interruptions, injection site changes, Cancer April 15, 2022 or switching to oral aprepitant; this illustrates clinical concerns with the use of injectable FosAPR, which is an unmet medical need. [5][6][7][8][9][10][11][12] Fosnetupitant (FosNTP) is the intravenously administered phosphorylated prodrug of netupitant. The active drug netupitant has a high binding affinity and selectivity for the NK 1 receptor, with an elimination halflife of approximately 70 hours in plasma.…”

Section: Introductionmentioning

confidence: 99%

A phase 3 safety study of fosnetupitant as an antiemetic in patients receiving anthracycline and cyclophosphamide: CONSOLE‐BC

Matsuura

Tsurutani

Inoue

et al. 2022

Cancer

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BACKGROUND: Fosnetupitant (FosNTP), an intravenous neurokinin 1 receptor antagonist, demonstrated a favorable safety profile with a potentially low risk of injection site reactions (ISRs) and promising antiemetic efficacy in patients receiving cisplatin-based highly emetogenic chemotherapy in a previous phase 2 study. We conducted a randomized, double-blind safety study to evaluate the safety profile of FosNTP, including ISRs, in patients receiving doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide (AC/EC) chemotherapy. METHODS: Patients scheduled to receive AC/EC were randomized 1:1 to receive 235 mg of FosNTP or 150 mg of fosaprepitant (FosAPR), both in combination with 0.75 mg of intravenous palonosetron and 9.9 mg of dexamethasone on day 1. The stratification factors were age category (<55 vs ≥55 years) and study site. The primary end point was the incidence of treatment-related adverse events (TRAEs) with FosNTP. RESULTS: Overall, 102 patients were randomized to FosNTP (n = 52) or FosAPR (n = 50), and all were treated with the study drug and evaluated for safety. The primary end point, the incidence of TRAEs, was similar with FosNTP (21.2%; 95% confidence interval [CI], 11.1%-34.7%) and FosAPR (22.0%; 95% CI, 11.5%-36.0%), with any-cause ISRs observed in 5.8% and 26.0% of patients, respectively, and treatment-related ISRs observed in 0% and 10.0%, respectively. The overall (0-120 hour) complete response (defined as no emetic event and no rescue medication) rate, standardized by age category in the full analysis set, was 45.9% (23 of 51 patients) with FosNTP and 51.3% (25 of 49 patients) with FosAPR. CONCLUSIONS: FosNTP demonstrated a favorable safety profile with a very low risk of ISRs in the AC/EC setting.

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“…Although chemotherapeutic drugs are effective at killing tumor cells, some have several drawbacks, including their nonselective distribution, drug toxicity, and unexpected side effects to normal tissues, which have limited these agents’ clinical use [1–3]. There were few effective anti-cancer drugs available that would specifically kill cancer cells and not damage normal cells.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-coated chitosan nanoparticles induce ROS-mediated tumor cell apoptosis and enhance antitumor efficiency by targeted drug delivery via CD44

et al. 2017

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BackgroundA targeted drug nanoparticle (NP) delivery system has shown potential as a possible cancer treatment. Given its merits, such as its selective distribution at tumor sites and its controllable drug release, drug-loaded NPs can be effectively delivered to selected organs and targeted cells, thus enhancing its antitumor efficiency and reducing its toxicity.MethodsWe reported that hyaluronic acid (HA)-coated chitosan NPs promoted the drug delivery of 5-fluorouracil (5-Fu) into tumor cells that highly expressed CD44.ResultsOur new findings suggested that HA-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS). Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells.ConclusionsBiocompatible and biodegradable HA-coated chitosan NPs were developed to encapsulate a chemotherapeutic drug (5-Fu) to enhance drug accumulation in tumor cells and to improve the agent’s antitumor efficiency by offering targeted drug delivery via CD44.

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Fosaprepitant dimeglumine for the management of chemotherapy-induced nausea and vomiting: patient selection and perspectives

Cited by 10 publications

References 30 publications

Structural insights of human N-acetyltransferase 10 and identification of its potential novel inhibitors

Structural insights of human N-acetyltransferase 10 and identification of its potential novel inhibitors

A phase 3 safety study of fosnetupitant as an antiemetic in patients receiving anthracycline and cyclophosphamide: CONSOLE‐BC

Hyaluronic acid-coated chitosan nanoparticles induce ROS-mediated tumor cell apoptosis and enhance antitumor efficiency by targeted drug delivery via CD44

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