RANDOMIZED, DOUBLE-BLIND COMPARISON OF A PROCHLORPERAZINE-BASED VERSUS A METOCLOPRAMIDE-BASED ANTIEMETIC REGIMEN IN PATIENTS UNDERGOING AUTOLOGOUS BONE-MARROW TRANSPLANTATION

Background. Highly emetogenic combination alkylator therapy is routine ly used in autologous bone marrow transplantation for treatment of eli gible patients with solid tumors. Antiemetic therapy remains less than optimal in this setting. Methods. One hundred twenty-six patients wit h cancer receiving high dose cisplatin, cyclophosphamide, and carmusti ne with autologous bone marrow support were randomized to receive one of four double-blinded antiemetic regimens: 4-day continuous infusion prochlorperazine (6 mg/m(2) intravenous [i.v.] loading dose followed b y 1.5 mg/m(2)/hour) or metoclopramide (80 mg/m(2) iv loading dose foll owed by 20 mg/m(2)/hr) each with either dronabinol 5 mg/m(2) or placeb o capsules for two doses before carmustine on the last day of chemothe rapy, All subjects received scheduled lorazepam and diphenhydramine th roughout the 4-day study period. Efficacy was measured by the Emetic P rocess Rating Scale and the Rhodes Index of Nausea and Vomiting (INV) Form 2. Results. One hundred six patients completed the study and were fully evaluable. The median number of emetic episodes on the metoclop ramide study arm were: 1 (0-7, day -6), 1 (0-6, day -5), 2 (0-9, day - 4), and 2 (0-10, with dronabinol day -3) or 2 (0-7, no dronabinol day -3) and on the prochlorperazine study arm were: 4 (0-12, day -6), 0 (0 -8, day -5), 0 (0-12, day -4) and 2.5 (0-9, with dronabinol day -3) or 2 (0-12, no dronabinol day -3). Metoclopramide was significantly bett er on the first day of therapy (day -6, P < .002) and prochlorperazine was significantly better on the third day of therapy (day -4, P < 0.0 02). There was no significant difference among any of the four arms on the last day of chemotherapy (day -3), or when the median number of e metic episodes over the total study period were compared. The patients ' assessment of nausea, vomiting, and retching on the INV Form 2 was c onsistent with the observer ratings. Toxicities requiring dose reducti on or discontinuation of antiemetic drugs included diarrhea, cardiac a rrhythmias, sedation, anxiety, and akathisia. Conclusions. Both metocl opramide and prochlorperazine in combination with lorazepam and diphen hydramine offer good control of nausea and vomiting although the sedat ion and low risk for cardiac toxicity limit the regimen to an inpatien t setting with close monitoring. No regimen was clearly superior durin g the entire treatment period but prochlorperazine offered more consis tent control after the first day.