Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.
BACKGROUND
This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy.


METHODS
This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L).


RESULTS
On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication.


CONCLUSIONS
This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.
Cunningham
D
D
Institute of Cancer Research, Sutton, Surrey, U.K.
Dicato
M
M
Verweij
J
J
Crombez
R
R
de Mulder
P
P
du Bois
A
A
Stewart
A
A
Smyth
J
J
Selby
P
P
van Straelen
D
D
Parideans
R
R
McQuade
B
B
McRae
J
J
D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D015994:Incidence; D008140:Lorazepam / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008787:Metoclopramide / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use
D000932:Antiemetics; D017294:Ondansetron; D003907:Dexamethasone; D008787:Metoclopramide; D008140:Lorazepam; D002945:Cisplatin