Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens.
The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy.
Cubeddu
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Department of Pharmacology, University of North Carolina, Chapel Hill.
Hoffman
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Fuenmayor
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Finn
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D003520:Cyclophosphamide