Antiemetics – current standards and open questions

Abstract

Chemotherapy induced nausea and vomiting (CINV) is among the most feared side effects of chemotherapy for cancer patients and is associated with significant deterioration in quality of life. The major risk factors for CINV are emetogenic potential of chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (younger age, female gender, history of motion sickness, alcohol consumption). The use of first generation 5-hydroxytryptanine (5-HT3) receptor antagonists (ondansetron, tropisetron, dolasetron and granisetron) in combination with dexamethason has significantly improved the control of acute CINV. Additional improvement in the control of acute and delayed CINV for highly and moderately emetogenic chemotherapy has been demonstrated recently with two newer antiemetic agents, a second generation 5-HT3 receptor antagonist palonosetron and neurokinin-1 (NK-1) receptor antagonist aprepitant. However, the role of palonosetron with respect to old 5-HT3 antagonists remains to be verified when both are combined with dexamethason in the first 24 hours and recommended therapies for delayed emesis. Aprepitant is a current standard of care for the prevention of acute and delayed CINV in patients receiving highly emetogenic chemotherapy. The value of this agent has been demonstrated also in breast cancer patients receiving anthracycline-based chemotherapy. Despite recent progress, a significant number of patients still develop CINV. To further improve control of acute and delayed CINV many questions remain to be addressed in ongoing and future properly designed randomized clinical trials. These include use of new antiemetic combinations as are palonosetron and aprepitant with current and other agents (olanzepin, gabapentin, midazolam, gherlin); new NK1 antagonists; single day vs. multiple days dosing of antiemetics and in different clinical settings (multiple days chemotherapy, bone marrow transplantation).