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.
OBJECTIVE
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.


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.


CONCLUSIONS
There was a significant improvement in CR rate with aprepitant combined with a 5HT3-RA and dexamethasone. Patient preference strongly favored the aprepitant cycle.
Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, 535 Barnhill Dr, RT #473, Indianapolis, IN 46202, USA.
Costantine
C
Albany
Mary J
MJ
Brames
Christopher
C
Fausel
Cynthia S
CS
Johnson
Joel
J
Picus
Lawrence H
LH
Einhorn
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000077608:Aprepitant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D009025:Morpholines; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077608:Aprepitant; D003907:Dexamethasone; D002945:Cisplatin