Rationale for the use of a single fixed intravenous dolasetron dose for the prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14 clinical trials.
Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous dolasetron dose group (who received actual doses of 88-112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).
Whitmore
J B
JB
Immunex Corporation, Seattle, WA 98101-2936, USA. jwhitmore@immunex.com
Kris
M G
MG
Hesketh
P J
PJ
Grote
T H
TH
DuBois
D M
DM
Cramer
M B
MB
Hahne
W F
WF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy; D011807:Quinolizines / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D011807:Quinolizines; C060344:dolasetron; D002945:Cisplatin