Aprepitant: the evidence for its place in the prevention of chemotherapy-induced nausea and vomiting

Chrisp, Paul

doi:10.2147/ce.s7420

Cited by 5 publications

(2 citation statements)

References 30 publications

(66 reference statements)

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“…In contrast, the expression of NK1R in normal non‐cancerous cell lines is not necessary for their viability, suggesting the specificity of NK1R antagonists against glioma cells. Aprepitant is a safe and well‐tolerated drug with good diffusion across the blood–brain barrier 25,49,50 . Previous studies have shown the benefits of aprepitant as an adjuvant against GBM.…”

Section: Discussionmentioning

confidence: 99%

“…Aprepitant is a safe and welltolerated drug with good diffusion across the blood-brain barrier. 25,49,50 Previous studies have shown the benefits of aprepitant as an adjuvant against GBM. For instance, the combination of aprepitant with an anti-HIV drug (maraviroc), which is an inhibitor of the C-C chemokine receptor 5 pathway, exerted synergistic GBM growth inhibitory effects.…”

Section: The Effects Of Aprepitant 5-ala and Their Combination On Flu...mentioning

confidence: 99%

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The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

et al. 2023

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Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti‐cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti‐cancer synergy of a clinically approved neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid (5‐ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U‐87 human GBM cells. We found that aprepitant and 5‐ALA effectively inhibited GBM cell viability. The combinatorial treatment of these drugs exerted potent synergistic growth inhibitory effects on GBM cells. Moreover, aprepitant and 5‐ALA induced apoptosis and altered the levels of apoptotic genes (up‐regulation of Bax and P53 along with downregulation of Bcl‐2). Furthermore, aprepitant and 5‐ALA increased the accumulation of protoporphyrin IX, a highly pro‐apoptotic and fluorescent photosensitizer. Aprepitant and 5‐ALA significantly inhibited GBM cell migration and reduced matrix metalloproteinases (MMP‐2 and MMP‐9) activities. Importantly, all these effects were more prominent following aprepitant–5‐ALA combination treatment than either drug alone. Collectively, the combination of aprepitant and 5‐ALA leads to considerable synergistic anti‐proliferative, pro‐apoptotic, and anti‐migratory effects on GBM cells and provides a firm basis for further evaluation of this combination as a novel therapeutic approach for GBM.

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Section: Discussionmentioning

confidence: 99%

Section: The Effects Of Aprepitant 5-ala and Their Combination On Flu...mentioning

confidence: 99%

The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

et al. 2023

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A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Kast¹,

Boockvar

Brüning³

et al. 2013

Oncotarget

151

147

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To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

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Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting

Langford¹

2010

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Introduction:The selective neurokinin-1 receptor antagonist aprepitant is effective in the treatment of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with both moderately and highly emetogenic chemotherapy. Fosaprepitant has been developed as an intravenous prodrug of aprepitant.Aims:To update the evidence underlying the use of fosaprepitant to prevent CINV.Evidence review:Aprepitant in combination with a serotonin antagonist and a corticosteroid controls acute and delayed symptoms of CINV in patients receiving moderately to highly emetogenic chemotherapy. Bioequivalence of fosaprepitant with aprepitant has recently been demonstrated, which has led to its inclusion in clinical guidelines for treatment of acute CINV with highly, and some regimens of moderately, emetogenic chemotherapy. Early studies of the clinical efficacy of fosaprepitant have shown improvement over treatment with ondansetron. Both aprepitant and fosaprepitant are well tolerated with most adverse events observed of mild or moderate intensity. Conflicting economic evidence has shown that whilst aprepitant provides an increased quality of life in patients treated for CINV, there are differing views over its absolute cost in relation to standard therapy. The incremental cost-effectiveness ratio of aprepitant, however, appears to lie within acceptable bounds.Place in therapy:Fosaprepitant and aprepitant are recommended in guidelines for preventing CINV due to moderately and highly emetogenic chemotherapy. Fosaprepitant is bioequivalent to aprepitant, and could offer potential benefits for patients who may be unable to tolerate oral administration of antiemetics during an episode of nausea or vomiting.

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Aprepitant: the evidence for its place in the prevention of chemotherapy-induced nausea and vomiting

Cited by 5 publications

References 30 publications

The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

The in vitro anti‐cancer synergy of neurokinin‐1 receptor antagonist, aprepitant, and 5‐aminolevulinic acid in glioblastoma

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting

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