Does Dexamethasone Enhance the Efficacy of Alizapride in Cis-Platinum-Induced Delayed Vomiting and Nausea?

Abstract

At the present time 5-HT₃ antagonists in combination with corticosteroids represent the best prophylaxis and treatment of acute vomiting and nausea in highly emetogenic cancer chemotherapy. However, 24 h after chemotherapy 5-HT₃ antagonists are no longer superior to benzamides for prevention of delayed symptoms. All recommendations for use of corticosteroids in delayed nausea and vomiting basically rely on one small study by Kris et al. [J Clin Oncol 1989;7:108–114]. Since the use of corticosteroids in cancer chemotherapy remains controversial, this single-blind, randomised, prospective trial was initiated to re-evaluate the benefits of corticosteroids during the days after chemotherapy. Thus patients treated for ovarian cancer received 5 mg tropisetron (Navoban^®) plus 20 mg dexamethasone for the prevention of acute vomiting and nausea in cis-platinum-containing chemotherapy (50 mg). Twenty-four hours after the beginning of chemotherapy 49 patients were randomised to receive 3 × 100 mg alizapride (Vergentan^®) plus a placebo medication (group A) and 47 patients to receive 3 × 100 mg alizapride plus 3 × 4 mg dexamethasone (group B) for 3 days depending on the incidence of acute vomiting beginning on day 2. The well-being of both groups was compared using objective and subjective parameters (Rotterdam Symptom Checklist). Major control of acute vomiting was achieved in 87.5% of the cases. The study was stopped after this interim analysis of 96 patients revealed no advantage of corticosteroids during the days after chemotherapy. Significant differences between both groups were detected only on a few days (day 6: objective nausea in favour of group A, day 4: objective vomiting in favour of group B, day 6: objective vomiting in favour of group A, day 3: constipation in favour of group A, days 4 and 5: difficulty concentrating in favour of group A, day 3: dry mouth in favour of group B). In contrast to acute nausea and vomiting the addition of corticosteroids is not beneficial in the prevention of delayed nausea and vomiting. Until better stretegies are available the best prophylaxis of delayed symptoms is the control of acute nausea and vomiting using 5-HT₃ antagonists plus corticosteroids. The use of benzamides has to be considered efficacious in the prevention of delayed vomiting and nausea.