Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms

Abstract

The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting

“…Referring to the work of Peterson et al (1996), we were also unable to detect differences between the control of delayed symptoms. Perhaps impaired control of delayed symptoms is a sequel of corticosteroid administration for prophylaxis of acute nausea and vomiting.…”

“…Earlier studies have mainly investigated different corticosteroid quantities in comparison with no or placebo medication. Prior work in this area suggests that especially patients with low prechemotherapy night-time cortisol excretion profit from cortisol administration (Fredrickson et al, 1992), that endogenous cortisol exerts antiemetic effects similar to that of exogenous corticosteroids (Hursti et al, 1993), and dexamethasone in high doses (20 mg) may impair the control of delayed symptoms (Peterson et al, 1996) whereas this adverse effect was not observed at doses of 8 mg (Carmichael et al, 1994).…”

Aspects of delayed chemotherapy-induced nausea

“…The mechanisms by which corticosteroids exert their antiemetic effect are largely unknown. In a previous study we found that a single dose of 20 mg dexamethasone enhanced the effect of 5-HT 3 receptor antagonists on acute emesis but impaired the control of delayed nausea occurring 3-5 days after chemotherapy [9]. There was a rapid recovery of the endogenous cortisol production in these patients but a direct relationship between cortisol levels and delayed nausea was not observed.…”

Symptom Documentation in Cancer Survivors as a Basis for Therapy Modifications

“…F or example, an episode of nausea may last for two hours and a period of delayed nausea after chemotherapy may be de ned as the days with at least one episode of nausea per day (23).…”