Significant progress has been made in recent years in developing more effective means of preventing
nausea and
vomiting induced by
cancer chemotherapy. With appropriate application of currently available
antiemetic regimens, the majority of patients with
cancer who are receiving
chemotherapy can anticipate experiencing no
emesis during their treatment. Nevertheless, incompletely controlled
emesis remains a problem for a significant percentage of patients. Persistent challenges include delayed
emesis and
emesis following high-dose
chemotherapy regimens. The goal of complete prevention of
emesis in all patients remains elusive. Therefore, there is a strong rationale for investigating new
antiemetic approaches. New
antiemetic agents currently under development target the
neurotransmitters serotonin (
5-hydroxytryptamine; 5-HT) and
substance P. A number of new selective antagonists of
serotonin 5-HT3 receptors are in clinical trials. Given the lack of clinically significant differences between the available
5-HT3 receptor antagonists, it appears unlikely that any of these new agents will have substantial advantages over currently approved agents. Several other
serotonin receptors have been targeted including the 5-HT4, 5-HT1A and 5-HT2A receptors. Of these approaches, only agonism of the
5-HT1A receptor has produced an agent that has proceeded into clinical testing. The most exciting new class of
antiemetics currently under development focuses on antagonism of the effects of the
neurotransmitter substance P. Results of early clinical trials with
tachykinin neurokinin NK1 receptor antagonists demonstrate enhanced control of acute
emesis with their addition to currently available agents and promising activity in controlling delayed
emesis. Available evidence would strongly suggest that this class of agents will represent the next important advance in efforts to control
nausea and
vomiting induced by
chemotherapy.