A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.
OBJECTIVE
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.


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.


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.
Nathan
P C
PC
Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. paul.nathan@sickkids.ca
Tomlinson
G
G
Dupuis
L L
LL
Greenberg
M L
ML
Ota
S
S
Bartels
U
U
Feldman
B M
BM
D000932:Antiemetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001499:Bayes Theorem; D001932:Brain Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007540:Isonipecotic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009325:Nausea / Q000139:chemically induced; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use*; D009864:Ontario; D010865:Pilot Projects; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000932:Antiemetics; D000970:Antineoplastic Agents; D007540:Isonipecotic Acids; C005260:metopimazine; D017294:Ondansetron; D003520:Cyclophosphamide; D002945:Cisplatin