Jaing, T.H., Tsay, P.K., Hung, I.J., Yang, C.P., & Hu, W.Y. (2004). Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia. Pediatric Hematology and Oncology, 21, 227–235.

To compare the efficacy of multidose ondansetron with single-dose granisetron in complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) receiving moderately emetogenic cyclophosphamide-based chemotherapy

Eligible patients entered a four-week run-in period during which they were given antiemetic agents according to the randomization scheme before their scheduled IV cyclophosphamide chemotherapy. Regimens were either single-dose granisetron (0.5 mg for patients weighing 25–50 kg or 1 mg for patients over 50 kg) administered orally one hour before chemotherapy or three doses of ondansetron (0.15 mg/kg administered IV one hour before chemotherapy and again four hours after the first dose with an additional oral dose eight hours after the first dose). Parents were asked to keep a log of their child’s emetic episodes during the first 24 hours following chemotherapy. Antiemetic efficacy was assessed by the number of vomiting episodes, the need for rescue medication, and the extent of nausea and appetite loss.

• N = 33
• MEAN AGE = 7.8 years (SD = 4.9 years)
• MALES: 64%, FEMALES: 36%
• KEY DISEASE CHARACTERISTICS: Patients with ALL receiving IV cyclophosphamide
• OTHER KEY SAMPLE CHARACTERISTICS: Ages 3–18 greater than 25 kg; no pre-existing chronic nausea or vomiting; and no coadministration of corticosteroids

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Taiwan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Single-institution, randomized, open-label, two-period crossover investigation

• Parents used a self-reported diary to document the number of emesis episodes.
• No other instruments or measurements were reported.
• No information was provided on how rescue medication, nausea, or appetite loss was measured.

In the granisetron arm, 20 out of 33 patients (60.6%) experienced complete efficacy compared to 15 out of 33 patients (45.5%) in the ondansetron arm, this was not statistically significant (p = 0.227). In both treatment groups, that males were less likely to respond to antiemetic treatment than females. In the granisetron group, 100% (12 out of 12) of females versus 76.2% (16 out of 21) of males experienced complete efficacy. In the ondansetron group, 100% (12 out of 12) of females versus 81% (17 out of 21) of males experienced complete efficacy. These differences did not meet a statistical significance (p = 0.271). The cost analysis demonstrated that granisetron costs about $0.20/kg (20 mcg/kg per patient), and ondansetron costs $20.09 per 8 mg vial or $6.18 per 4 mg tablet. This equates to about $0.99/kg (0.15 mg/kg per patient). The drug cost differential between the two modalities is $0.79/kg, favoring granisetron therapy on the basis of cost.

A single prophylactic oral dose of granisetron (10–20 mcg/kg) given prior to moderately emetogenic chemotherapy was at least as safe and effective as a triple dose of ondansetron given under similar circumstances. It also was more cost effective.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: Subjects were followed for only 24 hours. Time spent in the clinic (a reported purpose of the study) was not reported in the findings. Conversely, cost was reported in detail in the results section but was not listed as a purpose of the study.

Based on this study, a single dose of oral granisetron (10–20 mcg/kg) is as safe and effective as a triple dose of ondansetron for moderately emetogenic chemotherapy in children with ALL in the acute phase of chemotherapy-induced nausea and vomiting only. There seems to be a gender difference in antiemetic efficacy.