A number of clinical trials have only recently been conducted in the evaluation of
chemotherapy-induced
emesis prophylaxis. This is related to the development of new
antiemetic drugs, the 5-HT3 serotoninergic receptors antagonists which are very effective. Methodological principles of
drug development have been respected for the commercialization of this new class of
antiemetics. The essential phase I and II studies have allowed to establish the maximal tolerated doses and the efficacy-dose relation in order to conduct phase III clinical trials. At this time, the reference treatment for
emesis was
metoclopramide and thus, phase III trials have been initially conducted with this comparative treatment. These randomized studies have been carried out in parallel group and in double-blind in accordance with a methodology adapted to
cancer. The inclusion criteria have allowed to define an homogeneous population of
chemotherapy naive patients and clinical trials have been conducted with a stratification related to the
emetic power of the
chemotherapy. The number of patients to include in the studies was calculated related to the expected efficacy rates of the comparative drugs. The evaluation criteria of
nausea and
vomiting were standardized and the primary clinical end point to assess the efficacy of
antiemetic agents was determined by a complete control (no
emetic episode).
Nausea, which is a more subjective criterion, was assessed by the patient himself and the results could be included in the global analysis. Furthermore, the persistence of the efficacy over repeated courses has been assessed by clinical trials carried out on two to six cycles.