Understanding the pathobiology of chemotherapy-induced nausea and vomiting. Providing a basis for therapeutic progress.

Improved understanding of the physiologic and neuropharmacologic mechanisms underlying chemotherapy-induced nausea and vomiting (CINV) has driven significant progress in the treatment of CINV over the past 2 decades. Recognition of the role of neurotransmitters and their receptors in the process of CINV has been central to this progress. Initial attention focused on dopamine, then on serotonin, and most recently on substance P, which has yielded a useful new class of antiemetic medications known as selective neurokinin-1 receptor antagonists. Preclinical studies of these neurokinin-1 receptor antagonists suggested that they would demonstrate broad antiemetic activity in acute emesis, demonstrate activity against cisplatin-induced delayed emesis, be well tolerated, and contribute to enhanced efficacy when used in combination with other classes of antiemetics. These suggestions appear to have been largely borne out in clinical trials. Pharmacogenomics may offer a means to further extend and apply our understanding of CINV by enabling more selective targeting of antiemetic therapies. To date, the application of pharmacogenomics to CINV has focused on variations in the metabolism of serotonin receptor antagonists by CYP 450 genotype and variations in the 5-HT3 receptor gene itself.