title: Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy.
abstract: We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related.
authors.affiliation: Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.
authors.forename: G
authors.initials: G
authors.lastname: Fraschini
authors.forename: A
authors.initials: A
authors.lastname: Ciociola
authors.forename: L
authors.initials: L
authors.lastname: Esparza
authors.forename: D
authors.initials: D
authors.lastname: Templeton
authors.forename: F A
authors.initials: FA
authors.lastname: Holmes
authors.forename: R S
authors.initials: RS
authors.lastname: Walters
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D003520:Cyclophosphamide / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D004317:Doxorubicin; D003520:Cyclophosphamide