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. Rec ording of emesis and measurements of urinary 5-hydroxyindoleacetic aci d (5-HIAA), the main metabolite of 5-HT, was performed over 3 days. Co mparisons were performed for single-agent cisplatin (DDP) versus singl e-agent carboplatin (CBDCA), single-agent high-dose DDP (greater than or equal to 75 mg/m(2)) versus high-dose DDP combined with cyclophosph amide, high-dose versus low-dose DDP (less than or equal to 50 mg/m(2) ), 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 ex cretion induced by cisplatin was limited to day 1. Higher cisplatin do ses showed both a higher emetogenic potential and a more pronounced in crease in urinary 5-HIAA on day 1. No significant cant 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 sho wed a higher emetogenic potential than single-agent carboplatin. Low-d ose cisplatin induced less emesis than carboplatin combination therapy , but induced a larger increase in urinary 5-HIAA. Our findings provid e evidence for a relationship between emetogenic potential and pattern s of 5-HIAA excretion following platinum-based chemotherapy.