Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy.
OBJECTIVE
A number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis. This post-hoc analysis addressed whether: (1) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection (≥80% no emesis); (2) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk.


METHODS
Breast cancer patients in a phase III double-blind, placebo-controlled trial were randomized to antiemetic regimens including ondansetron and dexamethasone, or aprepitant, ondansetron, and dexamethasone. Multivariate logistic regression models were used to assess the impact on emesis (but not nausea) of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0-4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach.


RESULTS
Treatment with aprepitant (P < 0.0001), older age (P = 0.006), ethanol use (P = 0.0048), and no history of morning sickness (P = 0.0007) were all significantly associated with reduced likelihood of emesis. The proportion of patients with one, two, or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control (70.2-82.8% vs. 38.6-66.4%, respectively).


CONCLUSIONS
Aprepitant markedly improved control of emesis in patients with one or more risk factors. This analysis did not support using risk factors for modifying the antiemetic approach. A low-risk group with zero risk factors for whom aprepitant provided little benefit was of questionable clinical utility, since they comprised less than 3% of patients.
Warr
David G
DG
Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. david.warr@uhn.on.ca
Street
James C
JC
Carides
Alexandra D
AD
D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000077608:Aprepitant; D001943:Breast Neoplasms / Q000188:drug therapy; D018567:Breast Neoplasms, Male / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control; D064729:Neurokinin-1 Receptor Antagonists; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant; D017294:Ondansetron; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide
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