Oral dolasetron mesilate (MDL 73,147EF) for the control of emesis during fractionated total-body irradiation and high-dose cyclophosphamide in patients undergoing allogeneic bone marrow transplantation

The purpose of the present study was to evaluate the efficacy and safety of oral dolasetron mesilate in the prevention of nausea and vomiting that might otherwise be induced by total-body irradiation (TBI) and high-dose cyclophosphamide. In an open noncomparative study 20 patients who received TBI for 3 days and high-dose cyclophosphamide chemotherapy for 2 days as part of their preparation for bone marrow transplantation were given oral dolasetron mesilate at dosages ranging from 50 to 200 mg 1 h before each fraction of radiotherapy and cyclophosphamide administration. Initial rescue therapy consisted of intravenous dolasetron mesilate. If nausea and vomiting remained uncontrolled, standard antiemetics were to be used. Of the 20 patients, 13 had only two emetic episodes or fewer in the 3-day TBI period. On days 1 and 2 of cyclophosphamide administration, 11 and 6 patients had fewer than two emetic episodes. From day 1 to day 3, 15 patients experienced no nausea or only mild nausea, and on the days of chemotherapy 8 and 7 patients had mild nausea or none at all. Rescue with i.v. dolasetron mesilate was needed by 3 and 6 patients during the TBI and the chemotherapy periods respectively. In 2 patients additional antiemetics were used on days 2-3 and 4-5. Mild to moderate headache was reported in 6 patients. No unexpected abnormalities were observed in haematology, biochemistry or urinalysis, and vital signs were unaffected throughout the study period. The data suggest that oral dolasetron mesilate is effective and safe for the prevention of nausea and vomiting during TBI and cyclophosphamide chemotherapy prior to bone marrow transplantation. Future controlled studies should evaluate combination antiemetic therapy with dolasetron mesilate for this indication.