Use of an NK1 Receptor Antagonist to Prevent Delayed Emesis After Cisplatin

Kris, Mark G.; Radford, John; Pizzo, Barbara; Inabinet, Robin; Hesketh, Ann M.; Hesketh, Paul J.

doi:10.1093/jnci/89.11.817

Cited by 97 publications

(42 citation statements)

References 9 publications

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“…The most important effect of NK 1 -receptor antagonists is that they are able to markedly prevent both acute and delayed emesis induced by cisplatin in ferrets (79) and humans (80). As mentioned before, 5-HT 3 -receptor antagonists effectively prevent only acute emesis (43).…”

Section: Substance P and Its Receptormentioning

confidence: 86%

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

2003

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Abstract. The emetic response is primarily a protective reflex occurring in a wide variety of vertebrates in response to the ingestion of toxic compounds. The role of the nuclei in the brainstem, including the area postrema, nucleus tractus solitarius, the dorsal motor nucleus of the vagus, and the central pattern generator for vomiting, as well as the involvement of the abdominal visceral innervation relevant to the emetic reflex, have all been discussed by many researchers. The introduction of serotonin 5-HT 3 -receptor antagonists into clinical practice allowed for a dramatic improvement in the management of vomiting. However, vomiting still remains a significant problem. The mechanism of the emetic response is even more complicated than was first thought. This review attempts to bring together some of the evidence suggesting the roles of substance P and its receptor, neurokinin NK 1 receptor, in the brainstem nuclei in the development of emesis. Accordingly, NK 1 -receptor antagonists might represent novel drugs for the management of major types of emesis.

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Section: Substance P and Its Receptormentioning

confidence: 86%

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

2003

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“…The potential value of the NK 1 antagonists in the treatment of chemotherapy-induced emesis was first recognised in ferret studies, indicating that both acute and delayed cisplatin-induced emesis were completely abolished (Rudd et al, 1996). Preliminary observations suggested that similar benefits might be obtained in patients (Kris et al, 1997). A number of clinical studies have now confirmed the effectiveness of NK 1 antagonists both in the acute and, particularly, the delayed phase.…”

Section: New Developments: Nk 1 Antagonistsmentioning

confidence: 97%

Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

Wit

2003

Br J Cancer

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The advent of the 5HT 3 receptor antagonists (5HT 3 antagonists) in the 1990 s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase. 5HT 3 antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK 1 antagonists) belong to a new class of antiemetic agents that specifically target the NK 1 receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK 1 antagonists to dual therapy with a 5HT 3 antagonist plus dexamethasone improves the acute emesis protection by a further 10 -15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20 -30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled. Keywords: Antiemetics; 5HT 3 antagonists; NK 1 antagonists; neurokinine receptor antagonists; substance P Nausea and vomiting are considered as two of the most distressing side effects of anticancer chemotherapy. Chemotherapy-induced emesis has a serious impact on a patient's quality of life and the possibility to complete the planned chemotherapy successfully. Cisplatin is most commonly associated with profound nausea and vomiting, which follows a distinct pattern of an acute phase (0 -24 h after the start of chemotherapy) and a delayed phase that is mostly defined as occurring on days 2 -5 after the chemotherapy. Since severe emesis occurs in virtually all patients who receive a cisplatin dose of X50 mg m À2 , cisplatin-induced nausea and vomiting has served as the model to test anti-emetic agents for highly emetogenic chemotherapy Gralla et al, 1999). CURRENT ROLE OF 5HT 3 ANTAGONISTS PLUS DEXAMETHASONE; ACUTE PHASEBefore the advent of the 5HT 3 antagonists, nausea and vomiting were ranked as the two most distressing side effects of systemic chemotherapy (Coates et al, 1983). The use of 5HT 3 antagonists (ondansetron, granisetron and tropisetron) has provided complete acute emesis protection in 50-70% of patients receiving a first cycle of cisplatin-based chemotherapy . The addition of dexamethasone to 5HT 3 antagonists has improved the complete protection rate by a further 10 -15%, resulting in a total complete acute emesis protection in 65 -80% of patients .

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“…[14] The first NK-1 receptor antagonist (NK-1 RA) for human use was introduced in 1997. [15] Aprepitant, which is given orally, and its watersoluble prodrug fosaprepitant, given intravenously, are the only marketed drugs of this group at the moment, but several others will soon be registered. [16] One of them is casopitant, which has been proven to be effective for highly emetogenic chemotherapy (HEC) and MEC.…”

Section: Nk-1 Receptor Antagonistsmentioning

confidence: 99%

Corticosteroids, the oldest agent in the prevention of chemotherapy-induced nausea and vomiting: What about the guidelines?

Ryckeghem

2016

Journal of Translational Internal Medicine

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Chemotherapy-induced nausea and vomiting (CINV) remains one of the most disturbing side effects of cancer treatment. Research in antiemetic therapy has progressed gradually since the early eighties, and the development of antiemetic agents continues. This review focuses on the current management of CINV based on the most recent guidelines, and adherence to the latter is examined more carefully. Setrons (5HT3 receptor antagonists), corticosteroids, and NK-1 receptor antagonists are the cornerstones of antiemetic therapy. Corticosteroids are one of the oldest agents in the prevention of CINV. They are highly effective, increase the effect of other antiemetic agents, and are cost-effective. The latest developed 5HT3 receptor antagonist palonosetron led to an update of the guidelines of CINV. Other types include benzodiazepines, cannabinoids, and olanzapine. Various factors contribute to the overall risk of developing CINV, such as patient characteristics, emetogenic potency of the chemotherapeutic agents, and correct prevention of CINV. Current guidelines determine which is the right preventive regimen for each cancer patient at risk for experiencing CINV. Adherence to these guidelines and implementation in daily practice seem to be below the optimal level. In Belgium, authorities use the guidelines as a base for reimbursement and this has increased the level of implementation.

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Use of an NK1 Receptor Antagonist to Prevent Delayed Emesis After Cisplatin

Cited by 97 publications

References 9 publications

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

Roles of Substance P and NK1 Receptor in the Brainstem in the Development of Emesis

Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

Corticosteroids, the oldest agent in the prevention of chemotherapy-induced nausea and vomiting: What about the guidelines?

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