Matsuda, Y. Evaluation of the validity of chemotherapy-induced nausea and vomiting assessment in outpatients using the Japanese version of the MASCC antiemesis tool. Support Care Cancer 23, — Download citation. Received : 17 November Accepted : 17 May Published : 24 May Issue Date : November Anyone you share the following link with will be able to read this content:.
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References 1. Ann Oncol — Article Google Scholar 3. Ann Oncol — Article Google Scholar Upon exposure to chemotherapeutic agents, damaged enterochromaffin cells in the gastrointestinal tract release serotonin that subsequently binds to 5-HT3 receptors on the nearby vagal afferents in the abdomen.
The emetic center consists of a loosely organized network of neurons in the brain stem that receives signals not only from the gastrointestinal tract but also from other structures, such as the chemotherapy trigger zone in the area postrema [ 2 , 3 ].
These sensory signals are consolidated in the emetic center, leading to generation of efferent signals to the abdominal muscles, stomach, and diaphragm and subsequent emesis. The chemoreceptors of the area postrema are located outside the blood-brain barrier and can be directly activated by chemotherapeutic agents as well, triggering emesis. The neurotransmitter substance P, which is present in the peripheral and central nervous systems, is also released upon exposure to chemotherapy and binds to NK-1 receptors [ 4 ].
While serotonin is the primary mediator of emetic signals from the gastrointestinal tract, substance P appears to most commonly bind to NK-1 receptors within the central nervous system and elicit signals directly to the chemotherapy trigger zone and the emetic center of the brain, leading to delayed emesis.
However, substance P also acts in the gastrointestinal tract, potentially playing an auxiliary role in acute CINV. Crosstalk between 5-HT3 and NK-1 receptors has also been hypothesized, and may explain some differences among drugs [ 5 ]. Activation of one of these chemoreceptors may sensitize the vagus nerve to stimulation of the other receptor pathway and result in prolonged CINV. Prior to the s, antiemetic therapy consisted primarily of dopamine receptor antagonists such as metoclopramide, prochlorperazine, and haloperidol, and the use of glucocorticoids, such as dexamethasone [ 1 ].
Most of the research was aimed at reducing emesis during the acute phase 0 to 24 h after chemotherapy for newly emerging, highly emetogenic chemotherapeutic agents, including high-dose cisplatin. The s ushered in the development and approval of serotonin receptor antagonists and drastically improved the treatment of acute chemotherapy-induced emesis.
The U. Food and Drug Administration FDA approved the 5-HT3 receptor antagonist ondansetron in as prophylaxis for chemotherapy-induced emesis and approved granisetron and dolasetron for the same indication in The next landmark advance in CINV management came in with the approval of the second-generation 5-HT3 receptor antagonist palonosetron and the NK-1 receptor antagonist aprepitant [ 1 ]. Compared to the first-generation 5-HT3 receptor antagonists, palonosetron has a higher binding affinity to the 5-HT3 receptor and a half-life of 40 h versus 4 h, 7.
The chemical structure of palonosetron differs from the first-generation 5-HT3 receptor antagonists and this inhibitor not only blocks serotonin binding in an allosteric fashion but also leads to internalization of the 5-HT3 receptor and prevention of crosstalk with NK-1 receptors [ 5 ].
These characteristics may contribute to its increased efficacy against both acute and delayed emesis compared to the first-generation 5-HT3 receptor antagonists. The first NK-1 receptor antagonist, aprepitant, was also approved in [ 1 ]. While aprepitant had good oral bioavailability, central nervous system CNS penetrance, and high affinity for NK-1, it was poorly water soluble and required a special formulation [ 5 ]. Changes in the chemical structure resulted in the intravenous pro-drug fosaprepitant, which is water soluble and readily converts to aprepitant in vivo.
Newer oral NK-1 receptor antagonists have recently emerged, including rolapitant and netupitant in combination with palonosetron as the regimen NEPA. Rolapitant has a high CNS penetrance, high affinity and selectivity for NK-1, and a particularly long half-life h compared to 9—13 h for aprepitant [ 10 — 12 ]. Netupitant also has a high binding affinity for NK-1 and a half-life of 90 h.
These agents offer good tolerability and control of CINV. Each of these agents is discussed in further detail by Lee Schwartzberg in the third article of this supplement. There is a clear need for further improvements in the management of this bothersome side effect. Perhaps the greatest unmet need in CINV is the lack of complete nausea control [ 4 ]. While nausea and vomiting are often considered a unified symptom, the precise physiology and risk factors that contribute to nausea are poorly understood and many of the antiemetic agents currently available do little to relieve chemotherapy-induced nausea [ 4 ].
In addition, nausea can only be measured subjectively and may be underreported by patients and underestimated by clinicians [ 15 ]. These tools need to be used consistently to gain sufficient insight to inform antiemetic treatment decisions and minimize the risk of CINV.
Delayed CINV also continues to be an unmet clinical need. A more recent study of patients receiving MEC demonstrated significantly higher incidences of delayed nausea and vomiting compared to acute nausea and vomiting, with twice as many patients requiring rescue antiemetic therapy during the delayed phase [ 18 ].
It is important to note in both of these studies that although patients were receiving standard of care antiemetic therapy, at that time this did not include agents such as NK-1 receptor antagonists and olanzapine that have since demonstrated efficacy in preventing delayed CINV. Breakthrough and refractory CINV and anticipatory CINV present substantial clinical challenges in oncology as, once established, they are often difficult to reverse [ 4 , 19 ].
Breakthrough CINV despite appropriate antiemetic prophylaxis is difficult to control and can lead to treatment disruption and discontinuation. Breakthrough emesis can also lead to anticipatory CINV, with patients developing strong conditioned responses that have both a physiologic and psychologic component [ 4 ].
Patients who experienced CINV in their first cycle of chemotherapy were 3. Canon ink cartridge. Beanie Babies movie on Apple. Twee's return on TikTok. Windows Windows. Most Popular. New Releases. Desktop Enhancements. Networking Software. Trending from CNET. Developer's Description By Helsinn. Patients fighting cancer have to deal with Nausea and Vomiting, potential side effects related to chemotherapy. In this way the health care professional can promptly follow up and manage the symptom.
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