Antiemetic Prophylaxis with Fosaprepitant and 5-HT₃-Receptor Antagonists in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Abstract

Background

High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available.

Methods

A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8–32 mg/24h) or granisetron (2 x 40 µg/kg∙d⁻¹) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0–24h, >24–120h, >120–240h).

Results

Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (p>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0–24h (64 vs 22 events; p<0.01), >24–120h (135 vs 78 events; p<0.0001), >120–240h (268 vs 105 events; p<0.0001), and the whole observation period 0–240h (467 vs 205 events; p<0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24–120h (100% vs 74.3%) but not the other analyzed time periods (p>0.05).

Conclusion

The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.

Keywords:

• fosaprepitant
• 5-HT₃-antagonists
• pediatric
• antiemetic prophylaxis
• chemotherapy-induced nausea and vomiting
• autologous hematopoietic stem cell transplantation

Acknowledgments

The authors would like to thank the DRST Deutsches Register für Stammzelltransplantationen e.V., Essen, Germany and the PRST Kooperatives Pädiatrisches Register für Stammzelltransplantationen der Pädiatrischen Arbeitsgemeinschaft für Stammzelltransplantation und Zelltherapie (PAS&ZT) Deutschland for providing data on pediatric hematopoietic stem cell transplantation in Germany.

Abbreviations

µg per kg BW, microgram per kilogram bodyweight; 5-HT3, 5-hydroxytryptamine 3/serotonin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; autoHSCT, autologous hematopoietic stem cell transplantation; BW, bodyweight; CG, control group; CINV, chemotherapy-induced nausea and vomiting; FG, fosaprepitant group; h, hour(s); HSCT, hematopoietic stem cell transplantation; i.e., id est/that is to say; IV, intravenous; kg, kilogram; maximum, max; Mb., Morbus; mg, milligram; mg/dL, milligram per deciliter; minimum, min; mmol/L, millimole per liter; n, sample size; N, study cohort size; ns, not significant; NK1, neurokinin-1; p, probability value; PNET, primitive neuroectodermal tumors; POGO, Pediatric Oncology Group of Ontario; U/L, units per liter.

Compliance with Ethical Standards

This analysis was performed in accordance with the Helsinki declaration adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the 64th WMA General Assembly, Fortaleza, Brazil, October 2013. An ethics vote for the retrospective analysis was granted by the Ethics Committees of the University of Tübingen (775/2018BO2) and the Ludwig-Maximilian-University Munich (18-764). Formal consent is not required for this type of study. Baseline demographics, clinical factors and survival rates were abstracted from clinical and research records and maintained on a prospective basis. The legal basis for the data processing are Art. 6, 7, 9, 89 of the general data protection regulation (EU) 2016/679 of the EU in combination with §§ 4, 5, 6, 8, 9, 12, 13 of the Landesdatenschutzgesetzes Baden-Württemberg in its current form of May 25th, 2018.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare that they have no conflicts of interest.