Optimal Combination Therapy With Navoban(R) (Tropisetron) In Patients With Incomplete Control Of Chemotherapy-Induced Nausea And Vomiting

Even with the availability of potent and selective serotonin antagonists, chemotherapy-induced nausea and vomiting remain a major problem for many patients. This study aims to evaluate the benefit of combination therapy based on Navoban(R) (tropisetron) in patients who had incomplete control of nausea and/or vomiting induced by chemotherapy when using Navoban(R) as a single antiemetic agent. In their first chemotherapy course, 1072 patients planned to receive at least two identical cycles of emetogenic chemotherapy were treated with 5 mg Navoban(R) once daily, To evaluate three treatments additional to the recommended 5 mg once-daily Navoban(R) regimen during Course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of Course 1, a 2 x 2 x 2 factorial design was employed, Of these patients, 445 were centrally randomised to receive an additional dose of open-label dexamethasone (Day 1,0.2 mg/kg i.v,; Days 2-6, 8 mg p.o.) and/or open-label alizapride (Day 1, 100 mg i.v, and 4 x 50 mg p,o.; Days 2-6, 4 x 5 mg p.o.) and/or double-blind Navoban(R) - that is, doubling the dose to 10 mg once daily or placebo, Complete response rates during Course 1 (CRR, no nausea and no vomiting) were, for Day 1, 72% and for Days 1-6, 48%. More complete responders were observed when dexamethasone was added during Course 2, both on Day 1 (76% vs. 66%, p = 0.020) and on Days 1-6 (50% vs. 34%, p = 0.0004). With the addition of a conventional dose of alizapride, a moderate increase in CRR was observed; this was 75% vs, 68% (p = 0.14) on Day 1 and 47% vs. 37% (p = 0.041) on Days 1-6. CRR was not altered when the Navoban(R) dose was doubled. In patients incompletely controlled with Navoban(R) alone, the addition of dexamethasone significantly increased the CRR of both acute and delayed emesis (see Discussion),