Tsuji, D., Kim, Y.I., Taku, K., Nakagaki, S., Ikematsu, Y., Tsubota, H., … Daimon, T. (2011). Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial. Supportive Care in Cancer, 20, 1057–1064.

To determine the optimal IV granisetron dose, 1 or 3 mg, in patients with cancer receiving moderately emetogenic chemotherapy (MEC) or high emetogenic chemothrerapy (HEC)

Patients received 1 mg or 3 mg granisetron with adequate dosing of dexamethasone (20 mg IV dexamethasone on day 1 for patients receiving cisplatin-, anthracycline-, and cyclophosphamide-based regimens and 10 mg IV dexamethasone prior to chemotherapy for patients receiving MEC regimens). Granisetron and dexamethasone were diluted and administered 10-30 minutes before chemotherapy. Rescue antiemetic medication was possible, and the usage was recorded. Nausea and vomiting were recorded for seven days.

• This study reported on 359 patients.
• The age range of patients randomized to 1 mg granisetron group was 26–89 years old. The age range of patients randomized to 3 mg group was 22–84 years old.
• MALES (%)  overall 162 (45%); 3 mg cohort: n=25%; 1 mg cohort: n=21%   FEMALES (%) overall 197 (55%);  3 mg cohort: n=26%; 1 mg cohort: n=29%
• Cancer diagnoses were gastrointestinal, breast, lung, and other malignancies.

This was a multisite study conducted at 10 centers located throughout Japan. The setting type was not specified.

Patients were undergoing the active treatment phase of care.

This was a double-blind, randomized, noninferiority trial.

Patient diaries were used to record episodes of acute and delayed nausea, vomiting, use of rescue antiemetics, and bowel patterns.

Results indicated that 1 mg of granisetron was not inferior in effect to a 3-mg dose. The primary endpoint was the proportion of patients with a complete response during the first 24 hours after chemotherapy. For the primary endpoint, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p < 0.0001); however, results met the stated margin to demonstrate noninferiority. The secondary efficacy analysis showed that the maximum grade of nausea in the acute phase was similar in both groups (p = 0.61). In addition, no significant difference was found between the two groups in the number of vomiting episodes (p = 0.62). No statistically significant differences were observed in the maximum grade of nausea in the delayed phase (from day 2 to 7; p = 0.67). Adverse events on day 1 as well as on days 2–7 after chemotherapy were mild and not significantly different in both groups. No severe or unexpected adverse events were reported.

This study showed that 1 mg granisetron is not inferior to 3 mg when both doses are combined with dexamethasone, assuming that a 15% difference in complete response rate is accepted.

• The authors reported a limitation because of a wide delta margin (15%), however, a 95% confidence interval (CI) existed.
• Variation in chemotherapy regimens and diagnosis existed; these were not stratified to the two cohorts. Gender should have been stratified to the two cohorts as it is known that females experience nausea more often than males. Patients should also have been stratified according to the severity of their previous experience of CINV.

Findings suggest that lower dose granisetron may be effective for control of acute and delayed CINV.