Journal Article

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial

Biswas, Bivas, Bakhshi, Sameer, Sreenivas, Vishnubhatla, Batra, Atul, Dhawan, Deepa, Paul, Reeja

2015

Overview

Background Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. Methods A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5–18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15–40 kg = days 1–3, 80 mg; 41–65 kg = day 1, 125 mg and days 2–3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Results Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant ( p  = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p  < 0.001). No major adverse effects were reported by patients/guardians. Conclusions This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Activities of daily living / Administration, Intravenous / Adolescent / Adults / Analysis / Anti-Inflammatory Agents - therapeutic use / Antiemetics - therapeutic use / Chemotherapy / Child / Child health / Child, Preschool / Children / Clinical trials / Dexamethasone / Dexamethasone - administration & dosage / Dexamethasone - adverse effects / Dexamethasone - therapeutic use / Double-Blind Method / Female / Guardians / Hostility / Humans / Induction Chemotherapy / Male / Medical treatment / Medicine / Medicine & Public Health / Morpholines - therapeutic use / Nausea - chemically induced / Nausea - prevention & control / Neoplasms - drug therapy / Neurokinin-1 Receptor Antagonists - therapeutic use / Nursing / Nursing Research / Oncology / Ondansetron - administration & dosage / Ondansetron - adverse effects / Ondansetron - therapeutic use / Ontario / Original Article / Pain Medicine / Patients / Pediatrics / Placebo effect / Rehabilitation Medicine / Remission Induction / Serotonin 5-HT3 Receptor Antagonists - therapeutic use / Side effects / Therapy / Vomiting / Vomiting - chemically induced / Vomiting - prevention & control