Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy–induced vomiting in children: An open‐label, randomized phase 3 trial

Abstract

Background Breakthrough chemotherapy–induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open‐label, single‐center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV. Procedure Children aged 5‐18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms. Results Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm. Conclusion Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.

Efficacy of Olanzapine for High and Moderate Emetogenic Chemotherapy in Children

“…CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for nausea and vomiting. Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm [16].…”

“…However, few studies have focused on olanzapine use in children [2,3,16]. In Korea, the Korea Food and Drug Administration permits olanzapine administration only for pediatric psychiatric diseases; therefore, there is no reported evidence of its use as an AED in pediatric patients with cancer.…”

Antiemetic Regimen with Olanzapine in Pediatric Patients Receiving Highly Emetogenic Chemotherapy

“…11 However, recent research in India has already established olanzapine to be a useful agent for both prophylaxis and rescue therapy in pediatric CINV. 2,12,13 Notably, even with olanzapine, the CR rate achieved was only 70%. Nearly two-thirds of the patients also experienced significant nausea, and more research is required toward improving nausea control.…”

Medical Management of Inoperable Malignant Bowel Obstruction

“…Olanzapine, an atypical antipsychotic, has been validated to effectively reduce nausea and vomiting in patients with advanced-stage malignancy and incomplete bowel obstruction, with negligible treatment-associated toxicity, 46 and has been demonstrated to be significantly better than metoclopramide in the control of breakthrough chemotherapy-induced vomiting. 47,48 5-HT3 receptor antagonists (eg, ondansetron) and selective neurokinin-1 receptor blockers (aprepitant) are effective drugs for antiemetic therapy during chemotherapy, but they have not been well studied in the context of MBO. 49 No advice is available concerning the superiority of any of these antiemetics as a first-line treatment or whether they should be associated with other treatments.…”