The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group

Hesketh, Paul J.; Grunberg, Steven M.; Gralla, Richard J.; Warr, David; Roila, Fausto; Wit, Ronald de; Chawla, Sant P.; Carides, Alexandra D.; Ianus, Juliana; Elmer, M.; Evans, Judith K.; Beck, Klaus; Reines, Scott A.; Horgan, Kevin J.

doi:10.1200/jco.2003.01.095

Cited by 703 publications

(634 citation statements)

References 33 publications

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“…Nausea has not been signifcantly improved by the use of fosaprepitant (aprepitant) in 2 phase 3 studies of patients receiving cisplatin 22,23 and in 2 phase 3 studies of patients receiving an anthracycline and cyclophosphamide chemotherapy regimen. 24,25 Two reviews on the prevention of chemotherapy-induced nausea concluded that NK-1 receptor antagonists are not efective in controlling nausea.…”

Section: Discussionmentioning

confidence: 99%

Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting

Navari¹,

Nagy²,

Le‐Rademacher³

et al. 2016

J Community Support Oncol

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Section: Discussionmentioning

confidence: 99%

Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting

Navari¹,

Nagy²,

Le‐Rademacher³

et al. 2016

J Community Support Oncol

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“…Involvement of substance P and NK 1 has been suggested in the generation of delayed emesis following the treatment with chemotherapeutic agents (20). Recent studies further demonstrated the suppression of delayed emesis by aprepitant in both humans and animals (4,5,10), although brain-nonpenetrating NK 1 antagonists are ineffective (21). Cisplatin induced long-lasting emesis in ferrets for 72 h. T-2328 inhibited the cisplatin-induced delayed emesis by i.v.…”

Section: Gr73632-induced Foot Tapping In Gerbilsmentioning

confidence: 99%

“…NK 1 receptors are widely expressed throughout the central nervous system (3) and are involved in the regulation of various behavioral, endocrine, and autonomic functions. Based on the pharmacological data and recent clinical trials, it has emerged that blockade of brain tachykinin NK 1 receptors may provide a novel treatment of emesis (4,5), major depression (6), and anxiety problems (7). Therefore, there have been subsequent developments of selective and potent NK 1 -receptor antagonists (8).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Characterization of T-2328, 2-Fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile Dihydrochloride, as a Brain-Penetrating Antagonist of Tachykinin NK1 Receptor

Watanabe¹,

Asai²,

Ishii³

et al. 2008

J Pharmacol Sci

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Abstract. The pharmacological properties of T-2328 were evaluated as an antagonist of the tachykinin neurokinin 1 (NK 1 ) receptor. T-2328 inhibited the specific binding of [ 3 H][Sar 9 ,Met(O 2 ) 11 ]substance P to tachykinin NK 1 receptors in human lymphoblastic IM9 cells with K i of 0.08 nM. In the same assay, K i for aprepitant, a brain-penetrating NK 1 antagonist, was 1.3 nM. The antagonism of T-2328 is highly selective for the human NK 1 receptors since the affinities for human NK 2 , NK 3 receptors, and 13 other kinds of receptors and ion channels were >1000-fold lower than for NK 1 receptors. Reduction in Bmax with no change in affinity suggests the non-competitive nature of T-2328 interaction with the NK 1 receptor. T-2328 (0.03 -0.1 mg / kg, i.v.) and aprepitant (1 -3 mg / kg, i.v.) significantly prevented the GR73632 (i.c.v.)-induced foot tapping response in gerbils. The potencies of T-2328 in both in vitro and in vivo studies were more than 10 times greater than those of aprepitant. I.v. administration of T-2328 (0.1 -0.3 mg/ kg) potently blocked both acute and delayed emetic responses induced by cisplatin (5 mg / kg, i.p.) in ferrets. It is concluded that T-2328 is a potent, centrally active NK 1 antagonist. T-2328 may have potential as a novel therapeutic agent for the treatment of chemotherapyinduced emesis.

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“…Despite significant progress in the prevention of chemotherapyinduced nausea and vomiting (CINV), emesis continues to be associated with a significant deterioration in quality of life in patients treated with combination chemotherapy [3]. The addition of the brain-penetrant neurokinin-1 receptor antagonist (NK1-RA) aprepitant, to a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) and dexamethasone improved the prevention of CINV in patients receiving highly emetogenic single-day cisplatin chemotherapy [4][5][6]. In the Hoosier Cancer Research Network (HCRN), a phase III study was conducted with a 5HT3-RA plus dexamethasone plus either aprepitant or placebo in a randomized double-blind placebo controlled study of patients receiving 5 day cisplatin-based combination chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

Adra

Albany

Brames

et al. 2016

Support Care Cancer

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PurposeA phase III study adding aprepitant to a 5HTT3 receptor antagonist plus dexamethasone in germ cell tumor (GCT) patients treated with 5 day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single day cisplatin chemotherapy and is approved as a single-dose alternative. This single arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. MethodsGCT patients receiving 5 day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3 antagonist days 1-5 (days 1, 3, 5, if palonosetron) plus dexamethasone 20 mg days 1, 2, and 4 mg po bid days 6, 7, 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate -no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR>27%. Results65 patients were enrolled of whom 54 were eligible for analysis. Median age was 33. 51 patients received BEP (bleomycin, etoposide, cisplatin) chemotherapy. CR was observed in 13 (24.1%) patients (95% Agresti-Coull binomial C.I. 14.5%, 37.1%).

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The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group

Abstract: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

Cited by 703 publications

References 33 publications

Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting

Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting

Pharmacological Characterization of T-2328, 2-Fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile Dihydrochloride, as a Brain-Penetrating Antagonist of Tachykinin NK1 Receptor

Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

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