GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS:Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.
RCT Entities:
GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.
Authors: R J Gralla; D Osoba; M G Kris; P Kirkbride; P J Hesketh; L W Chinnery; R Clark-Snow; D P Gill; S Groshen; S Grunberg; J M Koeller; G R Morrow; E A Perez; J H Silber; D G Pfister Journal: J Clin Oncol Date: 1999-09 Impact factor: 44.544
Authors: C S Straathof; M J van den Bent; J Ma; P I Schmitz; J M Kros; G Stoter; C J Vecht; J H Schellens Journal: J Neurooncol Date: 1998-03 Impact factor: 4.130
Authors: Bas C Stunnenberg; Joost Raaphorst; Hans M Groenewoud; Jeffrey M Statland; Robert C Griggs; Willem Woertman; Dick F Stegeman; Janneke Timmermans; Jaya Trivedi; Emma Matthews; Christiaan G J Saris; Bas J Schouwenberg; Gea Drost; Baziel G M van Engelen; Gert Jan van der Wilt Journal: JAMA Date: 2018-12-11 Impact factor: 56.272
Authors: Elizabeth O Lillie; Bradley Patay; Joel Diamant; Brian Issell; Eric J Topol; Nicholas J Schork Journal: Per Med Date: 2011-03 Impact factor: 2.512
Authors: Bas C Stunnenberg; Willem Woertman; Joost Raaphorst; Jeffrey M Statland; Robert C Griggs; Janneke Timmermans; Christiaan G Saris; Bas J Schouwenberg; Hans M Groenewoud; Dick F Stegeman; Baziel G M van Engelen; Gea Drost; Gert Jan van der Wilt Journal: BMC Neurol Date: 2015-03-25 Impact factor: 2.474
Authors: Lee Schwartzberg; Meinolf Karthaus; Giorgia Rossi; Giada Rizzi; Maria E Borroni; Hope S Rugo; Karin Jordan; Vincent Hansen Journal: Cancer Med Date: 2019-04-09 Impact factor: 4.452
Authors: Robert S Phillips; Amanda J Friend; Faith Gibson; Elizabeth Houghton; Shireen Gopaul; Jean V Craig; Barry Pizer Journal: Cochrane Database Syst Rev Date: 2016-02-02