The relationship between parameters of serotonin metabolism and emetogenic potential of platinum-based chemotherapy regimens.
Evaluation of the relationship between parameters of serotonin (5-HT) metabolism and emesis in platinum-based chemotherapy. Female patients receiving chemotherapies containing either cisplatin (35 patients; 80 courses) or carboplatin (65 patients; 102 courses) were recruited. Recording of emesis and measurements of urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Comparisons were performed for single-agent cisplatin (DDP) versus single-agent carboplatin (CBDCA), single-agent high-dose DDP (> or = 75 mg/m2) versus high-dose DDP combined with cyclophosphamide, high-dose versus low-dose DDP (< or = 50 mg/m2), and single-agent CBDCA versus a combination with alkylating agents. Cisplatin induced both a significantly higher frequency of emesis and a significantly higher increase of 5-HIAA excretion than carboplatin. The velocity of 5-HIAA increase may correlate better with emetogenic potential than peak 5-HIAA excretion levels. The increase of 5-HIAA excretion induced by cisplatin was limited to day 1. Higher cisplatin doses showed both a higher emetogenic potential and a more pronounced increase in urinary 5-HIAA on day 1. No significant difference was found when single-agent cisplatin was compared with cisplatin combined with cyclophosphamide. In contrast, a combination of carboplatin with alkylating agents induced a larger increase in urinary 5-HIAA and showed a higher emetogenic potential than single-agent carboplatin. Low-dose cisplatin induced less emesis than carboplatin combination therapy, but induced a larger increase in urinary 5-HIAA. Our findings provide evidence for a relationship between emetogenic potential and patterns of 5-HIAA excretion following platinum-based chemotherapy.
du Bois
A
A
Department of Gnyecology, St. Vincentius Hospitals Karlsruhe, Germany.
Vach
W
W
Siebert
C
C
Holy
R
R
Ledergerber
M
M
Wechsel
U
U
Kriesinger-Schroeder
H
H
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine*; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced*
D018906:Antineoplastic Agents, Alkylating; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide