Effective Control of Moderate-Dose Cisplatin-induced Emesis by a Short-Course Regimen Including Metoclopramide, Chlorpromazine and Hydrocortisone: Results of a Randomized Trial with Metoclopramide Alone

Abstract

To improve the antiemetic effectiveness of a previously selected short regimen of moderate-dose metoclopramide (MCP), 80 patients were randomized to receive MCP either alone (regimen A) or in combination with low-dose chlorpromazine (CLP) and high-dose hydrocortisone (HDC) (regimen B) with the first course of cisplatin (50 mg/m2). The antiemetic effect was assessed over a 24-hour period only by objective means (duration and volume of vomiting in overnight fasting patients). The response was classified as follows: no emesis (absence of vomiting), partial protection (up to 100 ml of vomiting) and antiemetic failure (more than 100 ml). For regimen A, this study confirms the results previously reported over a 6-hour period. Regimen B provided better emetic control, significantly reducing the prevalence (p = 0.03) and severity (p = 0.02) of emesis, as well as the median volume (p less than 0.006) and duration (p less than 0.02) of vomiting. Except for the higher incidence of sedation, neither limiting nor unexpected toxicities were observed with the multidrug regimen. The male sex and antiemetic regimen B were the only favorable independent prognostic factors recognized by means of a multivariate analysis using a logistic model. This study therefore shows the usefulness of combining a lower dose of MCP and CLP, together with a high-dose HDC in a short regimen, suitable for outpatients receiving moderate-dose cisplatin. The better emesis control in the highly resistant group of female patients warrants further studies and a more aggressive approach.