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Chronic nausea occurs in most patients with advanced cancer. This study was done to assess the antiemetic effects of dexamethasone in patients with chronic nausea refractory to metoclopramide. Secondary outcomes included appetite, fatigue, and pain. Fifty-one patients who had nausea (> or = 3/10 on a 0-10 scale) for > or = 2 weeks despite 48 hours of oral metoclopramide therapy (40-60 mg/day) were enrolled. Patients received 20 mg/day dexamethasone (DM) orally (n = 25) or placebo (n = 26) for severe nausea in addition to metoclopramide (60 mg/day orally). At baseline the mean nausea intensity ratings in the DM and placebo groups were 8.0 and 7.4. At Day 8 they were 2.1 and 2.0, respectively. At Day 3 and Day 8, the mean difference in nausea intensity for the DM and placebo groups was 4.5 and 2.9 (P = 0.16) and 5.9 and 5.7 (P = 0.85), respectively. Improvement in appetite and fatigue were observed on Day 3 and Day 8 in both groups as compared with the baseline. Pain, vomiting, well-being, and quality of life remained unchanged in both groups at both times. We conclude that DM was not superior to placebo in the management of chronic nausea in our patients with advanced cancer.