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.

Keywords:

• fosaprepitant
• granisetron
• pediatric
• antiemetic prophylaxis
• chemotherapy induced vomiting
• children

Abbreviations

5-HT₃R, 5-hydroxytryptamine-3 receptor; ALL, acute lymphoblastic leukemia; ALT, alanine aminotransferase; AML, acute myeloid leukemia; ASCO, American Society for Clinical Oncology; AST, aspartate aminotransferase; BW, bodyweight; CG, control group; CINV, chemotherapy-induced nausea and vomiting; EP, emetogenic potential; FG, fosaprepitant group; IV, intravenous; kg, kilogram; L, liter; MASCC/ESMO, Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology; mg, milligram; µg, microgram; n, sample size; NK₁, neurokinin-1; NK₁R, neurokinin-1 receptor; p, p-value, probability value; U/L, units per liter; vs, versus.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

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