1238 A phase III randomized comparison of MDL (metoclopramide, dexamethasone, and lorazepam) plus granisetron with MDL alone in the prevention of nausea and vomiting associated with multi-day cisplatin-containing chemotherapy

Abstract

This study is designed to determine if the addition of granisetron, a potent serotonin-receptor antagonist, to the combination of metoclopramide, dexamethasone, and lorazepam (MDL) could improve the prevention of nausea and vomiting in patients receiving multi-day cisplatincontaining chemotherapy. One hundred and seventy one cancer patients receiving their initial combination chemotherapy including 20 mg/M of cisplatin daily for 5 days were randomized to receive metoclopramide (2 mg/kg × 2 I.V, DI-5), dexamethasone (8 mg × 1,4 mg × 2 IV, D1-2; 4 mg × 1,2 mg × 2 IV., D3-5), and lorazepam (1 mg × 1 p.o., DI-5) (MDL) or the identical MOL plus granisetron (3 mg × 1 Lv., 01-5) (MDL + G). Sixty six of 88 patients (75%)on MDL + G had fewer than three emetic episodes throughout the 5 days of study period, compared with 44 of 83 (53%) on MDL (P = 0.0027), and 52% of patients on MDL + G had no emetic episodes, compared with 35% on MDL (P = 0.022). The treatment failure rates were 16% in MDL + G arm and 27% in MDL arm (P = 0.12). Hiccup (27%), insomnia (11%), extrapyramidal symptoms (total 10%, dystonia 0.6%), facial flushing (9%), constipation (7%), and headache (6%) were the most common side effects. However, these were well tolerated and there was no significant difference in these side effects between the two arms. These results suggest that the addition of granisetron to standard MDL could safely improve the prevention of nausea and vomiting associated with multi-day cisplatin-containing chemotherapy. This study is designed to determine if the addition of granisetron, a potent serotonin-receptor antagonist, to the combination of metoclopramide, dexamethasone, and lorazepam (MDL) could improve the prevention of nausea and vomiting in patients receiving multi-day cisplatincontaining chemotherapy. One hundred and seventy one cancer patients receiving their initial combination chemotherapy including 20 mg/M of cisplatin daily for 5 days were randomized to receive metoclopramide (2 mg/kg × 2 I.V, DI-5), dexamethasone (8 mg × 1,4 mg × 2 IV, D1-2; 4 mg × 1,2 mg × 2 IV., D3-5), and lorazepam (1 mg × 1 p.o., DI-5) (MDL) or the identical MOL plus granisetron (3 mg × 1 Lv., 01-5) (MDL + G). Sixty six of 88 patients (75%)on MDL + G had fewer than three emetic episodes throughout the 5 days of study period, compared with 44 of 83 (53%) on MDL (P = 0.0027), and 52% of patients on MDL + G had no emetic episodes, compared with 35% on MDL (P = 0.022). The treatment failure rates were 16% in MDL + G arm and 27% in MDL arm (P = 0.12). Hiccup (27%), insomnia (11%), extrapyramidal symptoms (total 10%, dystonia 0.6%), facial flushing (9%), constipation (7%), and headache (6%) were the most common side effects. However, these were well tolerated and there was no significant difference in these side effects between the two arms. These results suggest that the addition of granisetron to standard MDL could safely improve the prevention of nausea and vomiting associated with multi-day cisplatin-containing chemotherapy.