Progress in the control of acute and delayed emesis induced by cisplatin

Ondansetron, a new 5-HT3 receptor antagonist, has been compared with high-dose metoclopramide in the control of acute emesis (24 h) induced by cisplatin (greater than or equal to 100 mg/m2). Ondansetron, given as three intravenous doses (0.15 mg/kg) 4-hourly, was superior to six intravenous doses of metoclopramide (2.0 mg/kg) in the control of acute emesis. Complete control of emesis was achieved in 40% of patients receiving ondansetron compared to 30% of patients receiving metoclopramide (P = 0.07); complete or major control (0-2 emetic episodes) was achieved in 65% and 51% of the patients receiving the two treatments respectively (P = 0.016). Patients entered in the acute emesis study who experienced no emesis or up to two episodes were randomised between placebo and ondansetron on day 2 to evaluate the control of delayed emesis up to day 5. Complete control of persistent or delayed emesis over days 2-5 was achieved in 59-78% of patients with oral ondansetron (16 mg t.d.s.) compared to 39-50% of patients receiving oral placebo. These differences failed to reach statistical significance except on day 4. Some patients with complete or major control of emesis on their first course of chemotherapy subsequently received further courses of ondansetron (median 3 courses; range 2-10) on a non-comparative basis. Similar control was achieved in 85% of courses. There may be some reduction in the degree of control with subsequent courses. Of 44 patients with complete control at cycle 1, 19 (44%) were emesis free and 3 (7%) experienced 1-2 episodes with cycle 3, though patients were sometimes withdrawn before cycle 3 for reasons other than inadequate anti-emetic control. Efficacy with successive courses can only be established in a prospective comparative trial. Both treatments were well tolerated but ondansetron caused significantly greater transient asymptomatic elevations in ALT/AST (P = 0.003/0.005). Acute dystonic reactions (2 patients) and akathisia (10 patients) occurred with metoclopramide only (P = 0.002). The role of ondansetron in the control of delayed emesis requires further study.