Concordance between substance P levels and antiemetic guidelines

9552 Background: While serotonin is believed to be the major mediator acute emesis, recent evidence suggests substance P (SP) is also involved in the pathogenesis of chemotherapy-induced vomiting. Research data accumulated over 18 months were used to analyze the degree of concordance between SP levels and the current antiemetic practice guidelines which incorporate the use of an NK1 receptor antagonist (RA). Methods: Levels of SP were measured in five blood samples obtained over 72 hours from 17 patients who received cisplatin-based chemotherapy regimens. Cisplatin doses ranged between 20–120 mg/m2. Each patient received a serotonin antagonist plus glucocorticoid; 15 patients also received an NK1 RA. Results: Analyses of the SP data were performed by: 1) phase of emesis; 2) cisplatin dose classified as Hesketh level 5 vs 4; and 3) cisplatin dose criterion utilized in the NK1 clinical trials. The mean change in SP (from baseline) in the acute and delayed phases was +9.1% and +31.5%, respectively. The trend of SP changes over 72 hours was similar regardless if the data were grouped by cisplatin dosages partitioned at 50 mg/m2 or 70 mg/m2. The least square mean changes in SP during the delayed phase were −28% and −25.8%, in patients receiving cisplatin dosages of <50 mg/m2 and <70 mg/m2, respectively. However, the absolute mean change between the acute and delayed phases was two-fold greater with data partitioned at < or ≥70 mg/m2 compared to < or ≥50 mg/m2. Clinically, 15 of the 17 patients had complete control of vomiting. None of the five patients who received <70 mg/m2, including two patients who did not receive the NK1 RA, experienced emesis during the entire study period. Conclusions: Measured levels of substance P: 1) support current practice guidelines related to the addition of an NK1 RA in patients receiving Hesketh level 5 cisplatin-containing regimens; 2) suggest that the likelihood of SP-mediated delayed emesis occurring is low with cisplatin dosages <70 mg/m2; and 3) provide biochemical justification for the cisplatin dosage criterion in clinical trials of the NK1 RA. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck