Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy.
BACKGROUND
An aprepitant (APR) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles.


METHODS
The authors performed a randomized, double-blind study. Eligible patients with breast carcinoma were naïve to emetogenic chemotherapy and treated with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND] 8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: OND 8 mg twice per day). Data on nausea, emesis, and use of rescue medication were collected. The primary end point was the proportion of patients with a complete response (CR; no emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple-cycle extension were the probabilities of a CR in Cycles 2-4 and a sustained CR rate across multiple cycles.


RESULTS
Of 866 patients randomized, 744 (85.9%) entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles. Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus 39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for Cycle 4. The cumulative percentage of patients with a sustained CR over all 4 cycles was greater with the APR regimen (P = 0.017).


CONCLUSIONS
The APR regimen was more effective than a control regimen for the prevention of nausea and emesis induced by MEC over multiple chemotherapy cycles.
Herrstedt
Jørn
J
Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark. jrhe@herlevhosp.kbhamt.dk
Muss
Hyman B
HB
Warr
David G
DG
Hesketh
Paul J
PJ
Eisenberg
Peter D
PD
Raftopoulos
Harry
H
Grunberg
Steven M
SM
Gabriel
Munir
M
Rodgers
Anthony
A
Hustad
Carolyn M
CM
Horgan
Kevin J
KJ
Skobieranda
Franck
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000077608:Aprepitant; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D009025:Morpholines; D000077608:Aprepitant