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

Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA; School of Pharmacy, West Virginia University, Morgantown, WV, USA; Department of Medicine, Section of Hematology-Oncology, West Virginia University, Morgan-town, WV, USA; WVU School of Pharmacy, Robert C. Byrd Health Sciences Center, PO Box 9520, West Virginia University, Morgantown, WV 26506-9520, USA ghiga{at}hsc.wvu.edu

Miklos L Auber, MD

Ramin Altaha, MD

Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA; Department of Medicine, Section of Hematology-Oncology, West Virginia University, Morgan-town, WV, USA

Debbie Piktel, BS

Department of Immunology and Microbiology, West Virginia University, Morgantown, WV, USA

Sohba Kurian, MD

Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA; Department of Medicine, Section of Hematology-Oncology, West Virginia University, Morgantown, WV, USA

Gerry Hobbs, PhD

Department of Community Medicine, West Virginia University, Morgantown, WV, USA

Kenneth Landreth, PhD

Department of Immunology and Microbiology, West Virginia University, Morgantown, WV, USA

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/m², 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.

Key Words: substance P • 5-HIAA • NK1 receptor • 5-HT3 receptor

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