5-hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: A URCC CCOP randomised controlled trial

Background: Despite widespread use of short-acting antagonists for the 5-hydroxytryptamine (5-HT) receptor, about 50% of patients given moderately emetogenic chemotherapy have delayed nausea. We aimed to assess whether a 5-HT-receptor antagonist was more effective than was prochlorperazine for control of delayed nausea and delayed vomiting caused by doxorubicin. Methods: 691 patients who previously had not had chemotherapy and who were scheduled to receive doxorubicin were given a short-acting 5-HT-receptor antagonist and dexamethasone before doxorubicin (day 1), and were randomly assigned to one of three regimens for days 2 and 3: 10 mg prochlorperazine taken orally every 8 h; any first-generation 5-HT-receptor antagonist (except palonosetron) taken as standard dose intravenously or orally; or 10 mg prochlorperazine taken as needed. Nausea and vomiting were assessed by use of a home record. The primary endpoint was mean severity of delayed nausea. The secondary endpoint was quality of life. Analyses were done by intention to treat. Findings: 519 (77%) of the 671 evaluable patients had delayed nausea, with a mean severity of 3·33 (95% CI 3·22-3·44). 161 (71%) of 226 patients assigned prochlorperazine every 8 h reported delayed nausea (mean severity 3·37 [3·16-3·58]), as did 179 (79%) of 226 patients assigned 5-HT-receptor antagonists (3·29 [3·09-3·48]) and 179 (82%) of 219 patients assigned prochlorperazine as needed (3·33 [3·15-3·50]); groups did not differ in mean severity (p=0·853, one-way ANOVA). Patients allocated prochlorperazine every 8 h had less delayed nausea than did those allocated 5-HT-receptor antagonists (p=0·05, t test) and those allocated prochlorperazine as needed (p=0·009, t test). Interpretation: Short-acting 5-HT-receptor antagonists are no better than is prochlorperazine in control of delayed nausea caused by doxorubicin. Although fewer patients taking prochlorperazine report delayed nausea, the proportion was unacceptably high.