Concordance between substance P levels and antiemetic guidelines.

Practice guidelines now include an antagonist of the substance P/NK1 (neurokinin 1) receptor pathway as part of the standard antiemetic regimen for patients receiving highly, as well as certain moderately, emetogenic chemotherapy regimens. Accumulated laboratory data were used to determine the degree of concordance between substance P levels and the current antiemetic guidelines. Five blood samples were collected over 72 hours from 22 adult patients treated with cisplatin-containing chemotherapy regimens. Overall, the mean baseline substance P level was 318 pg/mL. Although increases in substance P were observed during both phases of the emetic response, analysis by least squares means grouped by cisplatin dosage and vomiting phase was significantly different (P< 0.0001). Preliminary analysis of substance P levels appears to provide additional justification for including the NK1 receptor antagonist in the current antiemetic practice guidelines. In addition, these data provide biochemical justification for the cisplatin dosage criterion used in clinical trials.

5-Hydroxyindoleacetic acid and substance P profiles in patients receiving emetogenic chemotherapy.

BACKGROUND: Even though direct cause and effect has not been proved, clinical evidence suggests serotonin and substance P (SP) are involved in the emetic response following chemotherapy. Because of several parallels, we hypothesized that SP release, like serotonin, may be propagated by chemotherapy and both substances can be measured in biological fluids, and correlated with a particular phase of emesis. METHODS: Urinary 5-hydroxyindoleacetic acid (5-HIAA) was assessed by HPLC; serum and urine SP were measured by immunoassay. In addition to construction of neurotransmitter profiles, all SP data were grouped according to cisplatin dosages, = or >75 mg/m(2) versus <75 mg/m(2), and phase of emesis, acute versus delayed. Analyses of these data were performed by repeated measures analysis of variance. RESULTS: Samples were collected over a 72-hour period from 26 adult patients who received cisplatin- (n = 13) or non-cisplatin-containing (n = 13) chemotherapy. Mean baseline 5-HIAA: creatinine ratios were 5.23 and 5.16 in females and males, respectively; mean baseline SP levels were 392 and 181 pg/mL in females and males, respectively. Comparisons between SP data stratified by cisplatin dosage and emetic phase were significantly different, P < 0.0001. CONCLUSIONS: Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.