SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

The administration of platinum-based chemotherapy induces serotonin re lease from the enterochromaffin cells, causing nausea and vomiting. Th is study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the se rotonin type-3 antagonist tropisetron as an antiemetic agent. In nine chemotherapy-naive patients with disseminated germ-cell tumors, parame ters of serotonin metabolism in both blood and urine were evaluated du ring two consecutive courses of platinum-based chemotherapy. Serotonin concentrations in platelet-rich plasma and platelet-poor plasma as we ll as urinary 5-hydroxyindoleacetic acid (5-HIAA) and serotonin levels were measured during the full length of the courses. By means of comp arison with the antiemetic agent chlorpromazine, used on day I of the first course only, the effect of the serotonin type-3 antagonist tropi setron, the antiemetic agent used during the rest of the courses, on t hese parameters was studied. Clinical effects were also recorded. No c hange in the parameters of serotonin metabolism could be demonstrated during either course by the serotonin type-3 antagonist tropisetron. A lso in vitro, no effect of tropisetron on the active serotonin uptake by platelets was found. Serotonin levels in platelets showed no correl ation with emetic response. However, the platelet serotonin content de creased significantly between the first and the second course (P < 0.0 1). The significant reduction in platelet serotonin content observed b etween the first and the second course indicates a depletion of total body serotonin. The role of a serotonin type-3 antagonist might be aff ected by the altered serotonin equilibrium during later courses of che motherapy.