Corticosteroids
The mechanism of action of corticosteroids as antiemetics has not been fully determined. Some suggest that corticosteroids may decrease serotonin release, antagonize serotonin receptors, or activate corticosteroid receptors in the NTS of the medulla in the CNS.20 Many studies validate the effectiveness of corticosteroids in the prophylaxis of CINV symptoms. Efficacy with both dexamethasone and methylprednisolone has been described, but dexamethasone is much more widely studied and utilized. Dexamethasone improves the antiemetic control of serotonin antagonists by about 15% to 20%.20,21 In addition, dexamethasone is one of the cornerstone agents used to prevent delayed CINV. It is inexpensive and available in both IV and oral formulations.
The optimal dose of dexamethasone with different emetic stimuli has been studied in two controlled trials. For moderately emetogenic chemotherapy in the acute phase, a single 8-mg dose was as effective as larger doses or prolonged administration.33 In the setting of highly emetogenic cisplatin-based chemotherapy, higher doses of 12 or 20 mg were superior to doses of 4 and 8 mg.34 If used with aprepitant, the lower 12-mg prechemotherapy dose is recommended because of inhibition of steroid metabolism by aprepitant (see the neurokinin-1 receptor antagonist section).14 For prevention of delayed CINV symptoms, the most commonly used dose of dexamethasone is 8 mg twice daily on days 2 and 3 after chemotherapy without aprepitant. The dose should be reduced to 8 mg daily when used with aprepitant.
Corticosteroids are sometimes underutilized because of the potential risk of side effects. The adverse effects of corticosteroids include insomnia, jitteriness, increased appetite, GI distress, and perineal irritation if the IV dose is infused too quickly.20 For most patients, however, dexamethasone is well tolerated, especially because the therapy is typically short term at lower doses. Hyperglycemia can occur, especially in patients with pre-existing diabetes. These patients should be advised to monitor their glucose levels more frequently and contact their practitioner if the levels remain elevated. In the nondiabetic patient, hyperglycemia is rare. Tapering the corticosteroid dose after the end of treatment for CINV is usually unnecessary because the duration of therapy is short. Rare patients who have withdrawal-like symptoms may, however, benefit from a short taper.
Corticosteroids also have antitumor properties and are a part of the antineoplastic regimen for some malignancies, such as lymphoma, lymphoid leukemia, and myeloma. In these cases, no need is seen to administer additional dexamethasone for the antiemetic protection; however, the corticosteroid should be administered before the rest of the chemotherapy to provide antiemetic activity. If aprepitant is part of an antiemetic regimen in a situation where the corticosteroid is given for antitumor reasons, the dose of the corticosteroid should not be reduced.14
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