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

Purpose 5-Hydroxytryptamine-3 receptor antagonists (5-HT3 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-HT3 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-HT3 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-HT3 antagonists, as monotherapy or as adjunct treatment. Numbers of 5-HT3 antagonist unit doses per successfully treated patient were also calculated. Results Five studies (comprising 1,716 assessable patients) compared a 5-HT3 antagonist with placebo; five studies (2,240 patients) compared a combination of a 5-HT3 antagonist and dexamethasone with dexamethasone monotherapy. ARR for monotherapy was only 8.2% (95% Cl, 3.0% to 13.4%). On average, 74 5-HT3 antagonist doses must be administered to 12 patients (NNT, 12.2; 95% Cl, 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-HT3 antagonist did not significantly improve control of delayed emesis as compared with dexamethasone monotherapy (ARR, 2.6%; 95% Cl, -0.6% to 5.8%). Conclusion Neither clinical evidence nor considerations of cost effectiveness justify using 5-HT3 antagonists beyond 24 hours after chemotherapy for prevention of delayed emesis.