DRUG-TREATMENT OF CHEMOTHERAPY-INDUCED DELAYED EMESIS

Chemotherapy-induced emesis has a major adverse impact on patients und ergoing therapy for various malignancies, and this has led to consider able research in this field. Most investigative efforts have concentra ted on the acute phase of emesis that occurs within the first 24 hours after chemotherapy, and significant strides forward have been made wi th this problem. Better control of acute emesis with newer agents such as the serotonin 5-HT3 receptor antagonists has focused increasing at tention on a second phase of nausea and vomiting, known as delayed eme sis,which occurs more than 24 hours after chemotherapy. This delayed p hase is often not as well controlled with the antiemetics that have pr oven effective in acute emesis, and contributes to the distress associ ated with emetogenic chemotherapy. Most of the available data on delay ed emesis are based on studies with cisplatin-based regimens, with muc h less understanding of delayed nausea and vomiting induced by non-cis platin-based chemotherapy, Nevertheless, it is evident that the patter ns of delayed emesis associated with cisplatin and non-cisplatin chemo therapy have distinct differences. The control of delayed emesis, espe cially following cisplatin, remains a therapeutic challenge. Contribut ing to the lack of progress has been the absence of an experimental mo del to help in elucidating the pathophysiology of delayed emesis and i n the evaluation of new therapeutic approaches, The combination of met oclopramide and dexamethasone, although superior to placebo in randomi sed trials, provides only moderate control of delayed emesis following high-dose cisplatin. The 5-HT3 receptor antagonists that are effectiv e in the prevention of acute emesis with cisplatin have failed to make a major impact on the delayed phase. When combined with dexamethasone , these agents provide no additional benefit to that achieved using de xamethasone alone or dexamethasone combined with metoclopramide. With non-cisplatin chemotherapy, corticosteroids and 5-HT3 receptor antagon ists are the most useful agents. Efforts are ongoing to identify more effective treatments for delayed emesis. One novel approach involves t he blockade of substance P binding to neurokinin-1 (NK1) receptors. Th is article reviews what is currently known about chemotherapy-induced delayed emesis, with a focus on treatment strategies.