Randomized, double-blind, placebo-controlled, phase III cross-over study
evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3
receptor antagonist and dexamethasone in patients with germ cell tumors receiving
5-day cisplatin combination chemotherapy regimens: a hoosier oncology group
study.
Author(s): Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH.
Affiliation(s): Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, 535
Barnhill Dr, RT #473, Indianapolis, IN 46202, USA.
Publication date & source: 2012, J Clin Oncol. , 30(32):3998-4003
PURPOSE: Aprepitant, a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone are
standard antiemetic therapy for prevention of single-day, cisplatin-induced
nausea and vomiting. We conducted a double-blind, placebo-controlled phase III
cross-over study that compared aprepitant to placebo combined with standard
antiemetic prophylaxis (a 5HT3-RA and dexamethasone) in patients receiving 5 days
of cisplatin combination chemotherapy for testicular cancer.
PATIENTS AND METHODS: Patients receiving two consecutive identical courses of a
5-day cisplatin-based chemotherapy were randomly assigned to aprepitant 125 mg on
day 3 and 80 mg per day on days 4 through 7 or to placebo with the initial course
and crossover to the opposite treatment with the second course. The primary
objective was complete response (CR). Secondary end points were emetic episodes
(acute and delayed), nausea measurement based on a visual analog scale (VAS), and
patient-stated preference after the second study cycle.
RESULTS: In all, 71 patients were screened for the study and 69 were evaluable.
Thirty-five patients were randomly assigned to receive aprepitant and 34 to
receive placebo for the first course. Forty-two percent achieved CR with
aprepitant compared with 13% with placebo (P < .001). Eleven patients (16.2%) had
at least one emetic episode during the aprepitant cycle versus 32 patients
(47.1%) with placebo. Thirty-eight patients preferred the aprepitant cycle
whereas 11 preferred placebo (P < .001). There was no statistical difference in
VAS for nausea, but it was numerically superior with aprepitant. There was no
toxicity with aprepitant compared with placebo.
CONCLUSION: There was a significant improvement in CR rate with aprepitant
combined with a 5HT3-RA and dexamethasone. Patient preference strongly favored
the aprepitant cycle.
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