Comparison of granisetron plus dexamethasone versus an antiemetic cocktail containing midazolam and diphenhydramine for chemotherapy induced nausea and vomiting in children

Abstract

Background:Chemotherapy induced nausea and vomiting (CINV) is one of the most disturbing side-effects in children receiving highly emetogenic chemotherapy. We aimed to assess whether the addition of an antiemetic cocktail containing midazolam and diphenhydramine to granisetron plus dexamethasone combination could ameliorate CINV in this study.Patients and Methods:A total of 23 children aged between 1 and 16 years to receive cisplatin containing chemotherapy in our clinic were included in this study from April 2007 to April 2008. 76 cycles in 23 patients were randomly assigned to receive either antiemetic regimen 1 or antiemetic regimen 2. Antiemetic regimen 1 containing granisetron 0, 04 mg/kg plus dexamethasone 0, 2 mg/kg were given in 45 chemotherapy cycles. In 31 cycles, an antiemetic cocktail containing midazolam 0, 04 mg/kg, diphenhyramine 2, 5 mg/-kg in addition to granisetron plus dexamethasone was given. Number of vomiting, severity of nausea, the use of rescue therapy and adverse events were assessed between day 1 and day 5.Results:Complete response for the acute phase was observed 38/45 (84, 4%) cycles in regimen 1 as compared with 28/31 (90, 3%) in regimen 2, antiemetic cocktail regimen (P > 0.05). Complete response for delayed emesis after 24 h of the beginning of chemotherapy was observed in 29/45 (64, 4 %) in regimen 1 and 16/31 (51, 6%) in regimen 2. Antiemetic cocktail was not superior to the granisetron plus dexamethasone combination in controlling emesis in acute and delayed phase. Furthermore, patients receiving antiemetic regimen 2 were noted significantly more side effects.Conclusion:Our data showed that antiemetic cocktail containing midazolam and diphenhydramine was not better in controlling acute and delayed emesis. A slightly more toxicity with additional drugs was also observed.

Dexamethasone dosing for prevention of acute chemotherapy‐induced vomiting in pediatric patients: A systematic review

“…Of these, 16 studies (29 single-study arms) met our inclusion criteria ( Figure 1). 7,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Agreement between reviewers for inclusion of studies was almost perfect (kappa = 0.87; 95% CI: 0.75-0.98).…”

“…The evidence base that met the eligibility criteria consisted of 29 single-study arms, 25 of which were from 13 randomized trials. 7,[22][23][24][25][26][27][28][29][30][31][32][33] The other four single-study arms were from two noncomparative prospective studies 34,35 (N = 2) and one noncomparative retrospective study 36 (N = 2). Similar to how study arms from comparative studies were counted, complete acute CIV control was able to be determined for patients receiving HEC and MEC separately for the retrospective study and thus it was treated as having two study arms.…”

“…The sample sizes of the majority of included study arms were small: only six included ≥100 patients. 23,31,36 Of the 29 study arms included, 13 evaluated complete acute CIV control in patients exclusively receiving HEC, [22][23][24][25][26]35,36 eight in patients exclusively receiving MEC [25][26][27][28]30,36 and eight in patients receiving MEC or HEC that reported their findings as a single group and who for the purposes of this review were categorized as MEC. 7,29,[31][32][33][34] There was high heterogeneity in the study populations, cointerventions and outcomes between the dexamethasone dosing regimens evaluated, even when dichotomized based on the scaled recommended adult dexamethasone doses.…”

“…HEC : Of the 13 included study arms with patients receiving HEC, 12 evaluated a CPG-consistent antiemetic regimen. [22][23][24][25][26]35,36 The most common regimen used was dexamethasone in combination with a 5HT 3 antagonist alone (8 study arms), [22][23][24][25]35,36 followed by four study arms that evaluated dexamethasone in combination with a 5HT 3 antagonist plus aprepitant or fosaprepitant. 22,25,26 Only one study arm evaluated dexamethasone in a non-CPG-consistent regimen.…”

“…22,25,26 Only one study arm evaluated dexamethasone in a non-CPG-consistent regimen. 24 Five different total daily dexamethasone doses in eight study arms were given together with a 5HT 3 antagonist on day 1 of HEC: 6 mg/m 2 /day, 24 10 mg/m 2 /day, 23,36 13.5 mg/m 2 /day, 25 16 mg/m 2 /day, 35 and 27 mg/m 2 /day. 22 Complete acute CIV control rates of the two study arms using palonosetron 23 are presented in Table 3.…”