Aprepitant in pediatric patients using moderate and highly emetogenic protocols: a systematic review and meta‐analyses of randomized controlled trials

Okumura, Lucas Miyake; Rodrigues, Fernanda d’Athayde; Ferreira, Maria Angélica Pires; Moreira, Leila Beltrami

doi:10.1111/bcp.13193

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…Clinical drug-related side effects were similarly low in both groups. New or different safety issues were not observed in this study compared with previous studies with fosaprepitant in adult and pediatric patients [3, 4, 7, 12, 13].…”

Section: Discussioncontrasting

confidence: 64%

Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy – results of a non-interventional observation study

Willier¹,

Stanchi

Have³

et al. 2019

BMC Cancer

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BackgroundChemotherapy-induced nausea and vomiting (CINV) belong among the most burdensome side effects in hemato-oncology. Mostly, a combination of ondansetron and dexamethasone is used as antiemetic prophylaxis in pediatric patients undergoing emetogenic chemotherapy. However, dexamethasone is prohibited in different pediatric chemotherapy protocols. Currently, data on the use of ondansetron with the new antiemetic agent fosaprepitant without dexamethasone is not available for pediatric patients.MethodsIn this non-interventional observation study, 79 pediatric patients with a median age of 8.0 years (range 0.5–17.9 years) who received a CINV prophylaxis regimen with either fosaprepitant (4 mg/kg; maximum 150 mg) and ondansetron (as 24-h continuous infusion) (n = 40; fosaprepitant group/FG) or ondansetron only (n = 39; control group/CG) during moderately or highly emetogenic chemotherapy were analyzed. The groups were analyzed and compared for frequency of vomiting, administered doses of on-demand antiemetic dimenhydrinate and adverse events during the acute (0-24 h after chemotherapy administration) and delayed (> 24 h–120 h) CINV phases.ResultsA total of 112 and 116 chemotherapy blocks were analyzed in the fosaprepitant and the control group, respectively. The emetogenic potential of the administered chemotherapy did not significantly differ (p = 0.8812) between the two cohorts. In the acute CINV phase, the percentage of patients experiencing vomiting (n = 26 patients) and the vomiting events were significantly higher (p = 0.0005 and p < 0.0001, respectively) in the CG (n = 26 patients (66.7%); 88 events) compared with the FG (n = 10 patients (25.0%); 37 events). In the delayed CINV phase, the percentage of patients experiencing vomiting and the vomiting events were also significantly higher (p = 0.0017 and p < 0.0001, respectively) in the CG (n = 31 patients (79.5%); 164 events) compared with the FG (n = 17 patients (42.5%); 103 events). Additionally, significantly more dimenhydrinate doses were administered in the CG compared with the FG patients (n = 322/n = 198; p < 0.0001). The occurrence of adverse events did not significantly differ between the two groups (p > 0.05).ConclusionFosaprepitant (4.0 mg/kg) in addition to ondansetron, without application of dexamethasone, was well tolerated, safe, effective and superior to ondansetron only as CINV prophylaxis in pediatric patients during moderately and highly emetogenic chemotherapy.

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Section: Discussioncontrasting

confidence: 64%

Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy – results of a non-interventional observation study

Willier¹,

Stanchi

Have³

et al. 2019

BMC Cancer

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“…Among the AEs, the incidence of febrile neutropenia seemed higher with fosaprepitant (17.5%–23.3% across doses; apparently not dose related) than with the control regimen (11.4%); however, these results should be interpreted cautiously because this study was not powered to determine differences in the rates of febrile neutropenia between treatment groups. Although there are reports of increased incidence of febrile neutropenia with combination standard antiemetic therapy and NK 1 RA relative to standard antiemesis alone (conducted in either adult or adolescent patients), the majority of placebo‐controlled studies have found no significant difference in the rate of febrile neutropenia between antiemesis regimens with and without NK 1 RA, irrespective of patient age . Rates of neutropenia and pyrexia, also indications of infection, were similar between fosaprepitant and the control regimen (neutropenia: 20.0%–25.6% vs 25.7%; pyrexia: 7.0%–11.9% vs 11.4%).…”

Section: Discussionmentioning

confidence: 98%

Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy‐induced nausea and vomiting in pediatric cancer patients

Mora

Valero

DiCristina

et al. 2019

Pediatric Blood & Cancer

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Background Current antiemetic regimens are less effective in children than in adults. Fosaprepitant was recently approved for prevention of chemotherapy‐induced nausea and vomiting (CINV) in children aged six months and older. Procedure The pharmacokinetic (PK)/pharmacodynamic (PD) profile, safety, and tolerability of a single intravenous dose of fosaprepitant administered concomitantly with ondansetron with/without dexamethasone were evaluated in pediatric patients with cancer receiving emetogenic chemotherapy. PK/PD from three doses of fosaprepitant (3.0, 1.2, and 0.4 mg/kg, up to 150, 60, and 20 mg, respectively) were compared with placebo in 2‐ to 17‐year‐old subjects; an open‐label amendment evaluated a fourth dose (5.0 mg/kg, up to 150 mg) in those under 12 years old. Historical adult PK data were used for comparison. Efficacy was measured as an exploratory endpoint. Results PK data were evaluable for 167/234 subjects who completed cycle one. Aprepitant exposures were dose proportional; adolescents (12 to 17 years) receiving fosaprepitant 150 mg had exposures similar to adults at the same dose. Higher weight‐normalized doses (5 mg/kg) were necessary for children aged < 12 years to achieve comparable adult exposures. The adverse event profile was typical of cancer patients receiving emetogenic chemotherapy. Drug‐related adverse events were reported in 16 (6.8%) subjects, with hiccups being most common (n = 5; 2.1%). Conclusions Intravenous fosaprepitant was well tolerated by pediatric subjects with cancer, and dose‐proportional exposures were observed. Subjects < 12 years old required higher doses to achieve comparable adult exposures.

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“…32 New or different, potential, fosaprepitant-related adverse events, as described in previous studies, were not observed. 15,16,28,35 Since this study was conducted in a non-randomized, observational setup, the conclusions that can be drawn are limited. Due to inconsistencies in the chart documentation and the difficulties with younger pediatric patients (under 4 years of age) reporting nausea, a valid assessment of nausea was not possible.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Randomized clinical trials have proven the safety and good efficacy of a CINV prophylaxis regimen with aprepitant or fosaprepitant for adult and pediatric patients after emetogenic chemotherapy, during both the acute and delayed CINV phases. 13,15,16 However, there is few data on pediatric patients receiving an antiemetic prophylaxis with fosaprepitant during moderately or highly emetogenic chemotherapy. 11,16,17 Based on fosaprepitant's favorable properties, in terms of safety and efficacy, for adult patients and those of oral aprepitant in pediatric patients, the standard CINV prophylaxis regimen used for pediatric patients receiving moderately or highly emetogenic chemotherapy in the University Children's Hospital Tübingen was gradually changed from a regimen of granisetron with or without dexamethasone, to a prophylaxis regimen with additional single-dose intravenous fosaprepitant directly before the first administration in the respective chemotherapy course of a moderately or highly emetogenic chemotherapeutic agent.…”

Section: Introductionmentioning

confidence: 99%

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

Stanchi¹,

Ebinger²,

Hartmann³

et al. 2019

DDDT

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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-HT 3 R-antagonists and NK 1 R-antagonists. The NK 1 R-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.

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Aprepitant in pediatric patients using moderate and highly emetogenic protocols: a systematic review and meta‐analyses of randomized controlled trials

Cited by 12 publications

References 39 publications

Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy – results of a non-interventional observation study

Efficacy, safety and feasibility of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients receiving moderately and highly emetogenic chemotherapy – results of a non-interventional observation study

Pharmacokinetics/pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy‐induced nausea and vomiting in pediatric cancer patients

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

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