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.
Higa
Gerald M
GM
Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA; School of Pharmacy, West Virginia University, Morgantown, WV 26506-9520, USA. ghiga@hsc.wvu.edu
Auber
Miklos L
ML
Altaha
Ramin
R
Piktel
Debbie
D
Kurian
Sohba
S
Hobbs
Gerry
G
Landreth
Kenneth
K
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control / Q000652:urine; D011446:Prospective Studies; D013373:Substance P / Q000097:blood* / Q000652:urine*; D013997:Time Factors; D014839:Vomiting / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control / Q000652:urine
D000932:Antiemetics; D000970:Antineoplastic Agents; D015415:Biomarkers; D013373:Substance P; D006897:Hydroxyindoleacetic Acid; D002945:Cisplatin