NEW ORLEANSIt is possible to prevent most cases of chemotherapy-induced emesis by simple, convenient, and cost-effective regimens, Richard J. Gralla, MD, director of the Ochsner Foundation Cancer Institute, New Orleans, said at a cancer update sponsored by the Ochsner Medical Foundation and the American Cancer Society.
The three 5-HT3 serotonin receptor antagonistsondansetron (Zofran), granisetron (Kytril), and dolasetronprovide equivalent protection. The lowest maximally effective dose achieves the best result, and single-dose oral regimens are as effective as multiple-dose intravenous regimens, Dr. Gralla pointed out.
The 5-HT3 antagonists all do a terrific job at binding to the serotonin receptor. When you saturate the receptors, you achieve a threshold effect in which giving higher doses offers no advantage, he said. The same dose is used for patients receiving chemotherapy with moderate emetogenic potential as for those on agents with high emetogenic potential.
A number of comparative studies have found that the three agents offer virtually identical complete control of acute nausea and vomiting (within the first 24 hours after chemotherapy).
These drugs work not only within the vomiting center in the brain but also directly on the enterochromaffin cells in the gut, right where the drug is absorbed. This is why the oral form is as effective as intravenous delivery, since almost 100% of the drug is directly absorbed. Centers in the gut and in the brain are probably both important, Dr. Gralla said.
Adding a Corticosteroid
For patients with a moderate-to-high risk for emesis, the addition of 20 mg of dexamethasone enhances the antiemetic benefit of the 5-HT3 antagonist. A few personal factors can influence risk. For example, it is harder to control emesis in women and in younger patients, and easier to control emesis in persons who are heavy drinkers (even if they no longer drink alcohol), he said.
If a 5-HT3 antagonist is indicated, we always give a corticosteroid as well, unless there is a strong reason not to, Dr. Gralla said. The higher the patients risk, the greater the benefit of adding the corticosteroid. A single dose of dexa-methasone without the 5-HT3 agent can be used for patients with little risk for emesis but for whom you want to offer prevention, he added.
Besides its obvious benefit to the patient, the control of acute emesis also influences the occurrence of delayed emesis. When acute emesis is controlled, delayed emesis and anticipatory emesis are less likely to occur as well. Use your best antiemetic agents up front to prevent anticipatory emesis, especially with drugs such as high-dose cisplatin, he said.
Effective prevention of delayed emesis depends on giving the proper medications after chemotherapy. Single-agent therapy with corticosteroids offers some control, but is effective in only about 30% of cases. Combination therapy is superior, providing complete or major control in 50% of patients receiving emetogenic chemotherapy, he said.
The standard combination therapy for prevention of delayed emesis at Ochsner is 30 to 40 mg metoclopramide orally plus 8 mg dexamethasone orally, twice a day for 3 days, beginning 16 hours after chemotherapy. Though patients receiving only moderately emetogenic agents have less risk, it is still a good idea to treat them, and patients receive the regimen whether or not they experience acute emesis, he pointed out.
The results of metoclopramide plus dexamethasone are almost identical to those achieved with the 5-HT3 antagonists for complete control of delayed emesis; therefore, there is no reason to use these more expensive agents in this setting, he commented.