Advances in the management of nausea and vomiting induced by non-cisplatin containing chemotherapeutic regimens.

Nausea and vomiting are the most feared toxicities of chemotherapy. Afferent impulses from the chemoreceptor trigger zone, peripheral sites, the cerebral cortex, or the vestibular center can initiate the emetic reflex. Antiemetic protection therefore requires interruption of appropriate emetogenic pathways. Since the chemoreceptor trigger zone contains numerous dopaminergic neurons, antidopaminergic agents including phenothiazines and metoclopramide have gained importance as antiemetics. However standard dose phenothiazines have limited efficacy while high dose metoclopramide may have excessive toxicity in the non-cisplatin setting. Recent advances have therefore centered on development of new classes of antiemetics. Corticosteroids have excellent activity alone or in combination with other antiemetic agents. Cannabinoids have recently been introduced into commercial use as antiemetics with particular activity against non-cisplatin chemotherapy. Benzodiazepines are active against anticipatory nausea and vomiting and are also used in combination antiemetic regimens. Although the vestibular center seems to have a lesser influence on chemotherapy-induced nausea and vomiting, vestibular blocking agents such as scopolamine may have a potential role as adjunctive antiemetics. Finally, appreciation of the role of serotonin (5-HT3) receptors in both peripheral and central emetic pathways may lead to a new class of antiserotonergic antiemetic agents.