Use of an NK1 Receptor Antagonist to Prevent Delayed Emesis After Cisplatin

Abstract
Despite the use of serotonin antagonists, most patients continue to experience vomiting with chemotherapy, particularly delayed emesis. Substance P, a regulatory peptide (1), induces vomiting (2) and binds to the NK1 neuroreceptor. Compounds that block the NK1 receptor (36) lessen emesis after cisplatin, ipecac, copper sulfate, apomorphine, and radiation therapy (4,5). This broad activity suggests that substance P and the receptor may play central roles in emesis. We evaluated the NK1 receptor antagonist CP-122,721 in 17 cancer patients receiving cisplatin (⩾80 mg/m2 over 7) and delayed vomiting in 89% (8). CP-122,721 (1 mg/kg) prevented emesis after cisplatin in the ferret model that predicted the activity and dose of serotonin antagonists (9,10).