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

Costantine Albany, Mary J. Brames, Christopher Fausel, Cynthia S. Johnson, Joel Picus, Lawrence Einhorn

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58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3998-4003
Number of pages6
JournalJournal of Clinical Oncology
Volume30
Issue number32
DOIs
StatePublished - Nov 10 2012

Fingerprint

aprepitant
Germ Cell and Embryonal Neoplasms
Combination Drug Therapy
Cross-Over Studies
Cisplatin
Placebos
Serotonin 5-HT3 Receptor Antagonists
Receptors, Serotonin, 5-HT3
Nausea
Dexamethasone
Emetics
Antiemetics
Patient Preference
Visual Analog Scale
dexamethasone receptor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{4dc658231e0a4963a2f4ecebd441a508,
title = "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",
abstract = "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.",
author = "Costantine Albany and Brames, {Mary J.} and Christopher Fausel and Johnson, {Cynthia S.} and Joel Picus and Lawrence Einhorn",
year = "2012",
month = "11",
day = "10",
doi = "10.1200/JCO.2011.39.5558",
language = "English",
volume = "30",
pages = "3998--4003",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "32",

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TY - JOUR

T1 - 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

T2 - A Hoosier Oncology Group study

AU - Albany, Costantine

AU - Brames, Mary J.

AU - Fausel, Christopher

AU - Johnson, Cynthia S.

AU - Picus, Joel

AU - Einhorn, Lawrence

PY - 2012/11/10

Y1 - 2012/11/10

N2 - 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.

AB - 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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U2 - 10.1200/JCO.2011.39.5558

DO - 10.1200/JCO.2011.39.5558

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EP - 4003

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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ER -