Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications.
OBJECTIVE
5-Hydroxytryptamine-3 receptor antagonists (5-HT(3) antagonists) are effective for preventing acute chemotherapy-induced emesis but the benefits of continuing administration of these agents beyond 24 hours after chemotherapy (delayed emesis) remain unclear. The purpose of this study was to provide estimates of clinical efficacy and drug acquisition cost associated with administering 5-HT(3) antagonists beyond 24 hours, as monotherapy or as added to dexamethasone.


METHODS
This analysis is based on the Cancer Care Ontario Practice Guidelines Initiative meta-analysis of the efficacy of 5-HT(3) antagonists. Results from the clinical trials covered in that meta-analysis were reanalyzed to provide estimates of absolute risk reductions (ARR) and numbers needed to treat (NNT) for 5-HT(3) antagonists, as monotherapy or as adjunct treatment. Numbers of 5-HT(3) antagonist unit doses per successfully treated patient were also calculated.


RESULTS
Five studies (comprising 1,716 assessable patients) compared a 5-HT(3) antagonist with placebo; five studies (2,240 patients) compared a combination of a 5-HT(3) antagonist and dexamethasone with dexamethasone monotherapy. ARR for monotherapy was only 8.2% (95% CI, 3.0% to 13.4%). On average, 74 5-HT(3) antagonist doses must be administered to 12 patients (NNT, 12.2; 95% CI, 7.5 to 33.4) not receiving dexamethasone to protect one patient from delayed emesis. In those patients receiving dexamethasone as standard antiemetic treatment in the delayed phase, the addition of a 5-HT(3) antagonist did not significantly improve control of delayed emesis as compared with dexamethasone monotherapy (ARR, 2.6%; 95% CI, -0.6% to 5.8%).


CONCLUSIONS
Neither clinical evidence nor considerations of cost effectiveness justify using 5-HT(3) antagonists beyond 24 hours after chemotherapy for prevention of delayed emesis.
Geling
Olga
O
Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, USA.
Eichler
Hans-Georg
HG
D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D003907:Dexamethasone / Q000008:administration & dosage*; D016527:Drug Costs; D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D058831:Serotonin 5-HT3 Receptor Antagonists; D013997:Time Factors
D000932:Antiemetics; D000970:Antineoplastic Agents; D058831:Serotonin 5-HT3 Receptor Antagonists; D003907:Dexamethasone