Perugia Consensus Conference on Antiemetic Therapy

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Only the NCCN guidelines suggest dexamethasone as a possible combination partner for aprepitant with moderately emetogenic chemotherapy. In that study, aprepitant was given as monotherapy for the prevention of delayed CINV. This result might suggest that the combination of dexamethasone and aprepitant in the delayed phase would have greater antiemetic efficacy. This might be the reason for the NCCN panel recommending this combination in the moderately emetogenic setting in the delayed phase.

Further studies are warranted to clarify this clinically important question. When combined with aprepitant, dose reduction of dexamethasone dexamethasone is a sensitive substrate of the cytochrome P [CYP] 3A4 enzyme has to be undertaken. For the prevention of acute CINV, the dose of choice should be 20 mg of dexamethasone 12 mg when coadministered with aprepitant for highly emetogenic chemotherapy and a single 8-mg dose of dexamethasone 12 mg in the NCCN guidelines for moderately emetogenic chemotherapy Table 3.

These dose recommendations are largely driven by studies from the Italian Group for Antiemetic Research [ 18 , 19 ]. Aprepitant is the first representative of this new group that blocks the NK 1 receptor in the brainstem emetic center and gastrointestinal tract [ 20 ]. So far, it is only available for oral use and should be administered as indicated in Table 3 , as recommend by all three guidelines.

Published studies have demonstrated that the addition of an NK 1 RA to standard antiemetic therapy 5-HT 3 RA plus dexamethasone appears to have a significant effect in controlling cisplatin-induced acute as well as delayed emesis. In all studies, the comparative benefit of the aprepitant regimen was more pronounced in the delayed phase [ 20 — 22 ]. The use of aprepitant is unanimously suggested by all three guidelines for highly emetogenic chemotherapy and, in part, for moderately emetogenic chemotherapy.

In the moderately emetogenic setting, one study has been published so far, which formed the basis for the recommendation of aprepitant for anthracycline and cyclophosphamide—based emetogenic chemotherapy [ 17 ]. In that study, by Warr et al.

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The NCCN guidelines, however, recommended aprepitant in the moderately emetogenic setting in selected patients based on the emetogenic potential of the chemotherapy. In the MASCC guidelines, it was noted that no trial so far has compared aprepitant with dexamethasone for delayed emesis with the previous standard of dexamethasone combined with a 5-HT 3 RA in highly emetogenic chemotherapy [ 5 ].

In the meantime, a study that addressed this question was published by Schmoll et al.


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Aprepitant is a moderate inhibitor of CYP3A4; therefore, the dexamethasone dose has to be reduced, as discussed before. Theoretical concerns that aprepitant might interact with chemotherapeutic agents could not be demonstrated in preclinical and clinical studies so far [ 23 ]. Although metoclopramide was proven to be as effective as 5-HT 3 RAs when combined with steroids in the prevention of delayed CINV [ 24 , 25 ], it was not recommended again in the new guidelines in this setting.

It was stated that metoclopramide should be reserved for special circumstances, including known intolerance to 5-HT 3 RAs or steroids. However, because 5-HT 3 RAs are recommended as an alternative to dexamethasone in the delayed phase for moderately emetogenic chemotherapy, metoclopramide might also be an adequate alternative, although not recommended by the guidelines. A meta-analysis comparing the 5-HT 3 RAs with metoclopramide in the delayed phase for moderately emetogenic chemotherapy would be beneficial.

The combination of weak antiemetic efficacy with potentially beneficial side effects sedation, euphoria makes cannabinoids a useful adjunct to modern antiemetic therapy in selected patients. However, the associated side effects of dizziness and dysphoria should not be underestimated. Interestingly, in a systematic review of the efficacy of oral cannabinoids in the prevention of nausea and vomiting, it was found that cannabinoids were slightly better than conventional antiemetics e.

However, their usefulness was generally limited by the high incidence of toxic effects, such as dizziness, dysphoria, and hallucinations. All three guidelines unanimously suggest a combination of a 5-HT 3 RA, dexamethasone, and aprepitant within the first 24 hours for acute CINV with highly emetogenic chemotherapy Table 5.

Therefore, appropriate prophylaxis is indispensable. All three guidelines suggest the combination of dexamethasone and aprepitant for delayed CINV with highly emetogenic chemotherapy. All three guidelines recommend the combination of a 5-HT 3 RA plus dexamethasone with or without aprepitant for acute CINV with moderately emetogenic chemotherapy. However, the key question in this setting is whether aprepitant should be part of the antiemetic prophylaxis.

The NCCN guidelines, however, broaden the spectrum of the use of aprepitant in this setting and advise use in selected patients receiving other chemotherapies of moderately emetogenic risk e. Dexamethasone is the preferred agent to use for delayed CINV with moderately emetogenic chemotherapy. As discussed before, the NCCN guidelines suggest aprepitant with or without dexamethasone in this situation.

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A 5-HT 3 RA can be used as an alternative, although their therapeutic role in the delayed phase is rather limited [ 26 ]. In contrast to all three previously published guidelines, metoclopramide is not reflected in the new guidelines as an alternative option see above. The NCCN guidelines recommend prochlorperazine or metoclopramide as well, as alternative drugs to dexamethasone. All three guidelines suggest that, for patients treated with agents of low emetic risk, no antiemetic drug should be routinely administered before chemotherapy.

Breakthrough CINV is defined as an event that happens in spite of optimal preventive treatment. If optimal treatment has been given as prophylaxis, repeated dosing of the same agents is unlikely to be successful; the addition of dopamine-receptor antagonists metoclopramide might be useful, or adding other agents such as benzodiazepines or neuroleptics. The role of palonosetron, a new 5-HT 3 RA, has not yet been defined in this setting [ 5 ].

However, the NCCN guidelines advise the application of aprepitant for at least the first 3 days, in analogy to highly emetogenic chemotherapy. Furthermore, the NCCN guidelines explicitly mention palonosetron in this setting. Benzodiazepines can be a useful addition to antiemetic regimens in certain circumstances, such as anxiety and risk reduction of anticipatory CINV or in patients with refractory and breakthrough emesis, as suggested by all three guidelines.

Although often administered, studies with diphenhydramine or hydroxyzine in the prevention of CINV have not shown any antiemetic activity [ 4 ].


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Olanzapine, an atypical antipsychotic drug, has potential antiemetic properties because of its action at multiple receptor sites implicated in the control of nausea and vomiting [ 27 ]. In a phase II trial of olanzapine in combination with granisetron and dexamethasone for the prevention of CINV, the combination therapy proved to be highly effective in controlling acute and delayed CINV in patients receiving highly and moderately emetogenic chemotherapy [ 28 ]. Results for moderately emetogenic chemotherapy were similar. The latest phase II study by Navari et al. A dose of 2.

Treatment guidelines are important because they provide clinicians with a series of recommendations developed from the consensus opinions of international experts based on their interpretation of the most recent clinical trial data. However, the need for more effective practical implementation of treatment guidelines is crucial to improve the quality of care of cancer patients.

User Name Password Sign In. Telephone: ; Fax: ; e-mail: Karin. Accepted July 9, Previous Section Next Section. View this table: In this window In a new window. Table 1. Table 2. Table 3. Dolasetron All three guidelines recommend the same doses of dolasetron of mg or 1. Granisetron All three guidelines recommend granisetron at a dose of 1 mg or 0.

Palonosetron All three guidelines recommend palonosetron at a dose of 0. Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.

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Clin Cancer Res ; 9 : — Randomized comparison of the antiemetic effects of metoclopramide and electroacupuncture in cancer chemotherapy. Br J Clin Pharmacol ; 25 : — Electroacupuncture for control of myeloablative chemotherapy-induced emesis: a randomized controlled trial. Enhancement of the antiemetic action of ondansetron by transcutaneous electrical stimulation of the P6 antiemetic point, in patients having highly emetic cytotoxic drugs. Br J Cancer ; 64 : — Acustimulation wristbands for the relief of chemotherapy-induced nausea.

Altern Ther Health Med ; 8 : 56 — 57 59 — Randomized double-blind study of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy. Support Care Cancer ; 11 : — Acupressure for nausea: results of a pilot study. Oncol Nurs Forum ; 27 : 41 — Acupuncture prophylaxis of cancer chemotherapy-induced sickness. Magnetic disk applied on Neiguan point for prevention and treatment of cisplatin-induced nausea and vomiting.

J Tradit Chin Med ; 11 : — Klein J Griffiths P. Acupressure for nausea and vomiting in cancer patients receiving chemotherapy. Br J Community Nurs ; 9 : — Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. The use of nonpharmacologic techniques to prevent postoperative nausea and vomiting: a meta-analysis.

Anesth Analg ; 88 : — The status and future of acupuncture clinical research. J Altern Complement Med ; 14 : — Cochrane systematic reviews examine P6 acupuncture-point stimulation for nausea and vomiting. J Altern Complement Med ; 12 : — Josefson A Kreuter M. Acupuncture to reduce nausea during chemotherapy treatment of rheumatic diseases. Rheumatology Oxford ; 42 : — Acustimulation wrist bands are not effective for the control of chemotherapy-induced nausea in women with breast cancer. J Pain Symptom Manage ; 29 : — A progress study of cancer patients treated by acupressure for chemotherapy-induced vomiting after failure with the pharmacological approach.

Perugia Consensus Conference on Antiemetic Therapy

Minerva Med ; 98 : — Acupuncture to alleviate chemotherapy-induced nausea and vomiting in pediatric oncology—a randomized multicenter crossover pilot trial. Klin Padiatr ; : — User Account Sign In to save searches and organize your favorite content. Not registered? Sign up History 1 Recently viewed 1 Use of Acupuncture in Author: Ting Bao 1. Full access. How to write a great review. The review must be at least 50 characters long. The title should be at least 4 characters long. Your display name should be at least 2 characters long. At Kobo, we try to ensure that published reviews do not contain rude or profane language, spoilers, or any of our reviewer's personal information.

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Antiemetics in 5 Minutes! [Pharmacology]
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