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Aprepitant effective for CINV prevention in children
The addition of aprepitant to ondansetron effectively reduced or prevented chemotherapy-induced nausea and vomiting in pediatric patients who underwent moderately or highly emetogenic chemotherapy, according to results of a randomized, double blind phase 3 trial.
Oral aprepitant, a neurokinin-1 receptor agonist, often is combined with other antiemetic agents to help prevent chemotherapy-induced nausea and vomiting in adults. However, the safety and efficacy of this regimen in children has not been established, according to study background.
“Nausea and vomiting are common complications of cancer chemotherapy and can be particularly distressful and debilitating to pediatric cancer patients,” Stuart Green, MD, vice president of clinical research at Merck Research Laboratories and one of the researchers involved with the study, said in a press release. “Adding aprepitant to a standard regimen for prevention of chemotherapy-induced nausea and vomiting resulted in significant reduction of emetic events.”
Green and colleagues enrolled 302 patients aged 6 months to 17 years who were scheduled to receive moderately or highly emetogenic chemotherapy.
Researchers randomly assigned 152 patients to aprepitant (125 mg for those aged 12 to 17 years; 3 mg/kg up to 125 mg for those aged 6 months to < 12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for those aged 12 to 17 years; 2 mg/kg up to 80 mg for those aged 6 months to < 12 years) on days 2 and 3. The other 150 patients received placebo and ondansetron on day 1, followed by placebo on days 2 and 3.
The addition of dexamethasone was permitted.
Researchers stratified the cohorts according to patient age, planned use of chemotherapy associated with high risk of emetogenicity and planned use of dexamethasone. Treatment arms also were balanced with regard to prevalence of the most common malignancies, which included Ewing’s sarcoma, osteosarcoma, neuroblastoma, acute lymphocytic leukemia and rhabdomyosarcoma.
Complete response — defined as no vomiting, retching or rescue medication use within the first 5 days following chemotherapy initiation — served as the primary endpoint.
A significantly higher percentage of patients assigned aprepitant achieved a complete response in the acute phase (66% vs. 52%; P = .0135) and the delayed phase (51% vs. 26%; P < .0001).
A greater percentage of aprepitant-treated patients experienced no vomiting in the acute phase (71% vs. 53%; P = .0023) and delayed phase (55% vs. 28%; P ≤ .0001). Also, a higher percentage of aprepitant-treated patients reported no use of rescue medication in the acute phase (88% vs. 77%) and delayed phase (72% vs. 54%).
Incidence of adverse effects was comparable between study groups (aprepitant, 79%; control group, 77%). The most common all-grade adverse effects were anemia, febrile neutropenia and neutropenia.
Aprepitant-treated patients experienced a higher rate of grade 3 or grade 4 febrile neutropenia (15% vs. 14%). Patients in the control group experienced higher rates of anemia (17% vs. 9%) and decreased neutrophil count (11% vs. 7%).
Researchers acknowledged limitations of their study, including the fact use of rescue medications was not controlled, and the fact the study was not designed to assess aprepitant’s efficacy with specific chemotherapy regimens.
“Despite the lower absolute response observed in the present study versus historical data in adults, aprepitant still represents a clinically significant advancement in the pediatric and adolescent patient population, in which there is medical need for better prevention of nausea and vomiting,” Green and colleagues concluded. “Although the present data do not raise any specific [safety] concerns, longer term follow-up of pediatric patients treated with aprepitant-based anti-emetic regimens is needed.” – by Cameron Kelsall
Disclosure: Green reports employment with and stock ownership in Merck & Co. Two other researchers also report employment with Merck & Co.