Role of neurokinin-1 receptor antagonists in chemotherapy-induced emesis: summary of clinical trials.
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life, and although the use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, delayed nausea and vomiting remain a significant clinical problem. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when used in combination with dexamethasone compared to dexamethasone alone. The use of aprepitant in patients receiving moderately emetogenic chemotherapy will await the review and analysis of recently completed phase III trials. The control of nausea is improved in some studies with the use of aprepitant when it is combined with a 5HT3 receptor antagonist and dexamethasone, but nausea control remains suboptimal. The current data suggest that the mechanism of action of the NK-1s appears to be different from the 5-HT3 receptor antagonists. Future studies may explore the use of aprepitant and other NK-1s in moderately and highly emetogenic chemotherapy, as well in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.
Navari
Rudolph M
RM
Walther Cancer Research Center, University of Notre Dame, Notre Dame, Indiana 46556, USA. navari.1@nd.edu
D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077608:Aprepitant; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage*; D064729:Neurokinin-1 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D014839:Vomiting / Q000188:drug therapy*
D000932:Antiemetics; D000970:Antineoplastic Agents; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077608:Aprepitant