AN OPEN-LABEL DOSE COMPARISON STUDY OF ONDANSETRON FOR THE PREVENTIONOF EMESIS ASSOCIATED WITH CHEMOTHERAPY PRIOR TO BONE-MARROW TRANSPLANTATION

Nausea and vomiting are significant side effects in bone marrow transp lant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might imp rove emetic control, because of the high doses and combinations of che motherapy (CT) used in this setting. Our objective was to conduct a pr ospective, randomized study comparing two different administration met hods of high-dose ondansetron during a BMT preparative regimen in brea st cancer patients. Patients were eligible if they were nonpregnant wo men over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT=24 mg i.v. q 12 h/day) or continuous intraveno us infusion (CIV=8 mg i.v. loading dose followed by a continuous infus ion of 2 mg/h per day), A total of 66 patients were enrolled in the st udy (n=34, INT; n=32, CIV). There was no statistical difference betwee n treatment groups in the worst grade of emesis for the entire study p eriod (P=0.49). Greater than 90% of all patients were graded as failur es (25 emetic episodes or need for rescue antiemetics). Complete contr ol (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: gra de of emesis, episodes of vomiting and retching, nausea scores, and me an number of rescue medications administered. There were no difference s in efficacy when high-dose ondansetron was given as CIV or INT for t he control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate t o provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting var ious mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.