Prevention of acute emesis in cancer patients following high-dose cisplatin with the combination of oral dolasetron and dexamethasone.

PURPOSE: Dolasetron is a 5-HT3 antagonist antiemetic with active oral and intravenous formulations. The effects of this class are enhanced when combined with dexamethasone. This study tested the ability of the combination of oral dolasetron 200 mg and oral dexamethasone 20 mg to prevent acute emesis in cancer patients receiving initial cisplatin at doses > or = 70 mg/m2. Additionally, patients were randomly assigned to receive a second dosage of the regimen 16 hours later to improve control of acute symptoms. PATIENTS AND METHODS: A total of 75 patients were entered, with 38 randomized to the two-dose regimen. Thirty-five percent were women and 77% had lung cancer. RESULTS: Overall, the regimen prevented acute vomiting in 76% (95% confidence interval, 65% to 85%), including 74% of 35 patients who received cisplatin at doses > or = 100 mg/m2. There was no observed difference in emesis prevention between the one-dose (76%) and two-dose (76%) regimens (95% confidence interval for the difference, -20% to 19%). The median time to the onset of emesis was 19 hours for the one-dose regimen and 17 hours for the two-dose regimen in those patients with emesis. Headache occurred in 11% who received one dose and 16% who received two doses. CONCLUSION: The combination of oral dolasetron 200 mg and dexamethasone 20 mg given only once prevented acute emesis in 76% of patients who received cisplatin > or = 70 mg/m2. Administration of a second dose of the regimen did not improve the observed prevention rate or delay the time to emesis. This one-dose oral regimen has comparable or better effectiveness than reported results of intravenous combination regimens in preventing cisplatin-induced vomiting and merits further study and use.

Oral cisapride for the control of delayed vomiting following high-dose cisplatin.

Although combination antiemetics prevent vomiting during the initial 24 h after high-dose (> or =100 mg/m2) cisplatin, many patients experience delayed emesis 24-120 h afterwards despite receiving prophylactic dexamethasone and metoclopramide during this time. Cisapride is a prokinetic agent, which stimulates propulsive motility throughout the gastrointestinal tract without causing extrapyramidal effects. In this phase II trial, we tested the ability of cisapride to prevent delayed emesis following cisplatin. Twenty patients receiving initial cisplatin >100 mg/m2 were entered. All patients received intravenous dexamethasone with either metoclopramide or ondansetron to prevent acute emesis 0-24 h after receiving cisplatin. Patients who had experienced two or fewer acute vomiting episodes then received cisapride 20 mg orally four times daily for 4 days (24-120 h after cisplatin). Cisapride prevented delayed emesis in 2 patients (10%) during the entire 4-day period (95% confidence interval, 1-32%). Abdominal cramping and pain occurred in 35%. At the dose and schedule tested, oral cisapride prevented delayed emesis in only 10% of patients receiving cisplatin >100 mg/m2 and caused abdominal cramping in 35%. Since in prior trials among similar patients, placebo prevented delayed emesis in 11%, further study of cisapride and dose escalation for this indication are not recommended.