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Tropisetron plus haloperidol to ameliorate nausea and vomiting associated with high-dose alkylating agent cancer chemotherapy
Institution:1. Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85 Vinderen, Oslo 0319, Norway;2. Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway;3. Section of Pharmacogenetics, Department of Physiology and Pharmacology, Biomedicum 5B, Karolinska Institutet, Stockholm, Sweden;4. Department of Physiology, Faculty of Pharmacy, University of Belgrade, Serbia;5. NORMENT center, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway;6. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway;1. High Care Clinics, Mental Health Services Rivierduinen, Valklaan 3, Oegstgeest, 2342EB Leiden, The Netherlands;2. Mental Health Services North-Holland North, Alkmaar, The Netherlands;3. Bureau Beta, Nijmegen, The Netherlands;4. Moleman Research and formerly Radboud University, Nijmegen, The Netherlands;5. Academic Medical Centre, Amsterdam, The Netherlands;1. Dipartimento di Ingegneria, University of Campania “L. Vanvitelli”, Via Roma 28, 81031 Aversa, Caserta, Italy;2. J. Mike Walker ’66 Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843-3123, USA;3. Dipartimento di Strutture per l’Ingegneria e l’Architettura, University of Naples ”Federico II”, Via Claudio 21, Naples, Italy
Abstract:Tropisetron is a novel antiserotoninergic drug with potent and specific activity against cancer chemotherapy-induced emesis. High-dose cyclophosphamide or high-dose melphalan are chemotherapeutic regimens associated with severe nausea and vomiting refractory to current antiemetic medications. We compared in a randomised open label study the antiemetic efficacy of tropisetron and alizapride in a first group of 32 consecutive patients treated with high-dose alkylating agent chemotherapy with or without autologous bone marrow transplantation. Tropisetron was more effective than alizapride in reducing vomiting episodes. In the first 24 h of treatment the median number of episodes in patients treated with tropisetron was 5 compared with 9 episodes in the alizapride group (P = 0.005). In the 72 h study period the median number of emetic episodes was 6 in the tropisetron group and 12 in the alizapride group (P = 0.004). In a second group of 26 consecutive patients, a combination of tropisetron plus haloperidol, a dopamine antagonist, was employed for prevention of emesis. This combination was more effective than tropisetron as single agent in preventing emetic episodes, as the median number of emetic episodes in the 72 h of observation was only 3, while they were 6 in the tropisetron group. The side-effects of tropisetron were mild and reversible upon discontinuation of the drug. We conclude that tropisetron is an effective antiemetic drug when employed in high-dose alkylating agent chemotherapy, and that its activity is potentiated by the association with haloperidol.
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