Treatment with para-chlorophenylalanine antagonises the emetic response AND the serotonin-releasing actions of cisplatin in cancer patients

To test the role of serotonin in chemotherapy-induced nausea AND emesis, ten cancer patients were pretreated with the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). PCPA (2 g 8 hourly for 2 or 3 days prior to cisplatin) reduced the spontaneous urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), inhibited the increase in urinary 5-HIAA induced by cisplatin AND markedly attenuated the acute period of nausea AND vomiting associated with the cytotoxic drug. These results indicate that gastrointestinal serotonin mediates cisplatin-induced emesis AND that the amount of serotonin released by cisplatin is a major factor in determining the severity of the acute period of emesis experienced by the patient.