Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials.
BACKGROUND
The tendency of chemotherapeutic regimens to cause vomiting is dependent on the individual drugs in the regimen. The authors analyzed data combined from 2 Phase III trials to assess the effect of the neurokinin-1 (NK(1)) antagonist aprepitant combined with a 5HT(3) antagonist plus a corticosteroid in a subpopulation receiving > 1 emetogenic chemotherapeutic agent.


METHODS
In the current study, 1043 cisplatin-naive patients (42% were women) receiving cisplatin-based (> or = 70 mg/m(2)) chemotherapy were assigned randomly to a control regimen (ondansetron [O] 32 mg intravenously and dexamethasone [D] 20 mg orally on Day 1; D 8 mg twice daily on Days 2-4) or an aprepitant (A) regimen (A 125 mg orally plus O 32 mg and D 12 mg on Day 1; A 80 mg and D 8 mg once daily on Days 2-3; and D 8 mg on Day 4). Randomization was stratified for use of concomitant chemotherapy and female gender. The primary end point was complete response (no vomiting and no rescue therapy) on Days 1-5 (0-120 hours). Data were analyzed by a modified intent-to-treat approach, and logistic regression was used to make treatment comparisons among patients receiving the most frequently coadministered emetogenic concomitant chemotherapy (Hesketh level > or = 3).


RESULTS
Among the approximately 13% of patients (n = 81 for A; n = 80 for control) who received additional emetogenic chemotherapy (doxorubicin or cyclophosphamide), the aprepitant regimen provided a 33 percentage-point improvement in the complete response rate compared with the control regimen. Among the general population, the advantage with aprepitant was 20 percentage points.


CONCLUSIONS
The current analysis of > 1000 patients from 2 large randomized trials showed that in the subpopulation at increased risk of chemotherapy-induced nausea and vomiting due to concomitant emetogenic chemotherapy, the addition of aprepitant to standard antiemetics improved protection to an even greater extent than in the general study population.
Gralla
Richard J
RJ
New York Lung Cancer Alliance, New York, NY 10027, USA. rgralla@att.net
de Wit
Ronald
R
Herrstedt
Jorn
J
Carides
Alexandra D
AD
Ianus
Juliana
J
Guoguang-Ma
Julie
J
Evans
Judith K
JK
Horgan
Kevin J
KJ
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018943:Anthracyclines / Q000009:adverse effects; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000077608:Aprepitant; D002945:Cisplatin / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D009025:Morpholines / Q000627:therapeutic use; D009325:Nausea / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000627:therapeutic use; D058831:Serotonin 5-HT3 Receptor Antagonists; D014839:Vomiting / Q000517:prevention & control*
D000305:Adrenal Cortex Hormones; D018943:Anthracyclines; D000932:Antiemetics; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077608:Aprepitant; D017294:Ondansetron; D003907:Dexamethasone; D003520:Cyclophosphamide; D002945:Cisplatin