Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy.
OBJECTIVE
This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy.


METHODS
Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire.


RESULTS
Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated.


CONCLUSIONS
The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.
Warr
David G
DG
Princess Margaret Hospital, Medical Oncology, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. david.warr@uhn.on.ca
Hesketh
Paul J
PJ
Gralla
Richard J
RJ
Muss
Hyman B
HB
Herrstedt
Jørn
J
Eisenberg
Peter D
PD
Raftopoulos
Harry
H
Grunberg
Steven M
SM
Gabriel
Munir
M
Rodgers
Anthony
A
Bohidar
Norman
N
Klinger
George
G
Hustad
Carolyn M
CM
Horgan
Kevin J
KJ
Skobieranda
Franck
F
D000328:Adult; D000932:Antiemetics / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000077608:Aprepitant; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000627:therapeutic use; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced* / Q000517:prevention & control*; D017294:Ondansetron / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control*
D000932:Antiemetics; D009025:Morpholines; D000077608:Aprepitant; D015251:Epirubicin; D017294:Ondansetron; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide