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

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.

• Authors: Karin Melanie Cabanillas Stanchi, Martin Ebinger, Ulrike Hartmann, Manon Queudeville, Judith Feucht, Michael Ost, Marie-Sarah Koch, Carmen Malaval, Markus Mezger, Sarah Schober, Simone Weber, Sebastian Michaelis, Veit Lange, Peter Lang, Rupert Handgretinger, Michaela Döring
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 13 Pg. 3439-3451 ( 2019) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 31686784 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2019 Cabanillas Stanchi et al.

Chemical References

• Antiemetics
• Morpholines
• fosaprepitant
• Dexamethasone
• Granisetron

Topics

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