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Antiemesis guidelines stress use of new agents: new drugs may prevent nausea and vomiting in patients on emetogenic chemotherapy regimens.

HOLLYWOOD, FLA. -- New antiemetic agents, which can provide relief from nausea and vomiting in a wider array of patients than ever before, should be incorporated as preventive measures in chemotherapies that have a moderate or high risk of emesis, according to new guidelines issued by the National Comprehensive Cancer Network.

Nausea and vomiting remain among the top three most distressing side effects of emetogenic chemotherapy, despite the use of 5-H[T.sub.3] receptor antagonists for preventing emesis. Dr. David S. Ettinger said at a conference of the network.

Physicians and nurses tend to overestimate a patient's ability to control emesis. In one study, 83% of physicians and nurses felt that patients had control of emesis, but only 72% actually did. Similarly, 91% of physicians and nurses felt that patients had control over delayed emesis, but only 59% could control it, said Dr. Ettinger, chair of the 17-member antiemesis panel.

Many cancer patients experience nausea despite receiving prophylaxis. In one study of 360 chemotherapy-naive patients treated with doxorubicin, cisplatin, or carboplatin, 76% developed nausea after the first cycle of treatment despite use of the 5-H[T.sub.3] receptor antagonist ondansetron (Zofran) and the steroid dexamethasone. Emesis developed after the first cycle in 30% of patients. Nearly the same rate of events was reported after the second cycle (Cancer 97[11]:2880-86, 2003).

Researchers do not know which neurotransmitters are the most important in the brain's emetic center. One of the new antiemetic drugs, aprepitant (Emend), is an antagonist of the NK-1 receptor. This receptor normally binds the neurotransmitter called substance P, which is known to induce emesis in ferrets and dogs, panel member Dr. Mark G. Kris said.

In patients given a high dose of cisplatin, 48% of patients given standard prophylaxis with ondansetron and dexamethasone will not have emesis or need rescue treatment, compared with 68% of patients given a triple therapy of aprepitant, ondansetron, and dexamethasone. Aprepitant has similar efficacy in preventing both acute or delayed emesis.

Regimens with the standard 5-H[T.sub.3] receptor antagonists ondansetron, dolasetron (Anzemet), or granisetron (Kytril) prevent emesis in about 30% more men than women. But men and women benefit equally from regimens that include aprepitant. "This benefit in women is unique in the prevention of emesis," noted Dr. Kris, chief of the thoracic oncology service at Memorial Sloan-Kettering Cancer Center, New York.

Aprepitant is not a substitute for dexamethasone or a 5-H[T.sub.3] receptor antagonist, and is not a treatment of any kind. There are "absolutely no data that [aprepitant] or any other [drug] is a treatment for emesis once it has happened. We can prevent it, but we don't have a way to treat it," he said.

A new 5-H[T.sub.3] receptor antagonist, palonosetron (Aloxi), appears to have higher activity than other 5-H[T.sub.3] receptor antagonists. It has a 40-hour half-life--about five times longer than other agents--and a higher binding affinity. In trials involving chemotherapy with moderate risk of emesis, 46%-47% of patients who received 0.25 mg or 0.75 mg palonosetron alone responded completely to treatment during the first 5 days after chemotherapy, compared with 34% of patients who received 100 mg dolasetron.

On high emetic risk chemotherapy, 40%-42% of patients have had complete responses to 0.25 mg and 0.75 mg of palonosetron. Only 33% of patients who received 32 mg of ondansetron plus dexamethasone had complete responses after 5 days. Patients who received dexamethasone along with palonosetron or ondansetron obtained similar results.

Dr. Kris warned that palonosetron is not a substitute for dexamethasone or aprepitant, and it is not a treatment for emesis.

Patients should be protected from emesis throughout the full period in which they are at risk, said Dr. Ettinger of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore.

Dr. Ettinger and Dr. Kris each receive research support from, are consultants for, and are on the speakers' bureau of many of the manufacturers of antiemetic drugs.

The guidelines stress that prophylaxis should be maintained for at least 4 days for patients who receive chemotherapy with a high or moderate risk of emesis, Dr. Ettinger said.

For chemotherapy with high emetic risk, the guidelines recommend starting antiemetics before chemotherapy each day that chemotherapy is given. The guidelines recommend aprepitant on days 2-3, dexamethasone on days 2-4, and a choice of one of the four 5-H[T.sub.3] receptor antagonists: ondansetron (given days 2-4), granisetron (days 2-4), dolasetron (days 2-4), or palonosetron (only day 1). Lorazepam may be added if necessary.

Dexamethasone should not be given for antiemetic prophylaxis of any chemotherapy regimen if the regimen includes a corticosteroid, Dr. Ettinger said.

On the first day of chemotherapy regimens with moderate emetic risk, the guidelines advise administering dexamethasone and one of the four 5-H[T.sub.3] receptor antagonists with or without lorazepam before starting chemotherapy. Aprepitant is reserved for only selected patients at this stage.

Days 2-4 of emesis prevention in chemotherapy with a moderate emetic risk can involve one of the following: a lower dose of dexamethasone; ondansetron, granisetron, dolasetron, or metoclopramide with or without diphenhydramine; if aprepitant was used on day 1, a lower dose of aprepitant may be administered with dexamethasone on days 2-3; lorazepam may be added to any of the antiemetic regimens if necessary.


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Title Annotation:Clinical Rounds
Author:Evans, Jeff
Publication:Internal Medicine News
Geographic Code:1USA
Date:Jun 15, 2004
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