Efficacy, Safety And Feasibility Of Antiemetic Prophylaxis With Fosaprepitant, Granisetron And Dexamethasone In Pediatric Patients With Hemato-Oncological Malignancies

Drug Des Devel Ther. 2019 Sep 30:13:3439-3451. doi: 10.2147/DDDT.S214264. eCollection 2019.

Abstract

Background: Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HT3R-antagonists and NK1R-antagonists. The NK1R-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant.

Methods: This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts.

Results: Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%).

Conclusion: Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.

Keywords: antiemetic prophylaxis; chemotherapy induced vomiting; children; fosaprepitant; granisetron; pediatric.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Antiemetics / administration & dosage
  • Antiemetics / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Granisetron / administration & dosage
  • Granisetron / therapeutic use*
  • Humans
  • Male
  • Morpholines / administration & dosage
  • Morpholines / therapeutic use*
  • Nausea / chemically induced
  • Nausea / drug therapy*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*

Substances

  • Antiemetics
  • Morpholines
  • fosaprepitant
  • Dexamethasone
  • Granisetron

Grants and funding

This work was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany and the Förderverein für Krebskranke Kinder Tübingen e.V., Tübingen, Germany.