ORAL DOLASETRON MESILATE (MDL-73,147EF) FOR THE CONTROL OF EMESIS DURING FRACTIONATED TOTAL-BODY IRRADIATION AND HIGH-DOSE CYCLOPHOSPHAMIDEIN PATIENTS UNDERGOING ALLOGENEIC BONE-MARROW TRANSPLANTATION

The purpose of the present study was to evaluate the efficacy and safe ty of oral dolasetron mesilate in the prevention of nausea and vomitin g that might otherwise be induced by total-body irradiation (TBI) and high-dose cyclophosphamide. In an open noncomparative study 20 patient s who received TBI for 3 days and high-dose cyclophosphamide chemother apy for 2 days as part of their preparation for bone marrow transplant ation were given oral dolasetron mesilate at dosages ranging from 50 t o 200 mg 1 h before each fraction of radiotherapy and cyclophosphamide administration. Initial rescue therapy consisted of intravenous dolas etron mesilate. If nausea and vomiting remained uncontrolled, standard antiemetics were to be used. Of the 20 patients, 13 had only two emet ic episodes or fewer in the 3-day TBI period. On days 1 and 2 of cyclo phosphamide administration, 11 and 6 patients had fewer than two emeti c 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 peri od. The data suggest that oral dolasetron mesilate is effective and sa fe for the prevention of nausea and vomiting during TBI and cyclophosp hamide chemotherapy prior to bone marrow transplantation. Future contr olled studies should evaluate combination antiemetic therapy with dola setron mesilate for this indication.