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

Extract

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 (3–6) 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 <3 hours) that induces acute vomiting in 98% of the patients not receiving antiemetics (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).

All 17 patients had a normal electrocardiogram, bilirubin level, and creatinine level and provided written informed consent. A single oral dose of CP-122,721 (50 mg [n = 3], 100 mg [n = 4], and 200 mg [n = 10]) was administered 30 minutes before cisplatin. Patients were observed for 24 hours for emesis, nausea (11), and side effects and were contacted later about delayed vomiting. Statistical tests were two-sided.