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