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Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial

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Abstract

Background

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years.

Methods

A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5–18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15–40 kg = days 1–3, 80 mg; 41–65 kg = day 1, 125 mg and days 2–3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase.

Results

Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians.

Conclusions

This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

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Funding

Drug and placebo were supplied by Dr. Reddy’s Laboratories Ltd., Hyderabad, India. However, they were not involved in study design or analysis.

The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Contribution

Sameer Bakhshi: Literature search, figures, study design, data collection, data analysis, data interpretation, writing.

Atul Batra: Literature search, figures, data analysis, data interpretation, writing.

Bivas Biswas: Literature search and study design.

Deepa Dhawan: Blinding, randomization, figures, data collection, data analysis, data interpretation, writing.

Reeja Paul: Data collection and writing.

Vishnubhatla Sreenivas: Literature search, figures, study design, data analysis, data interpretation, writing.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sameer Bakhshi, Atul Batra, Bivas Biswas, Deepa Dhawan & Reeja Paul

  2. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India

    Vishnubhatla Sreenivas

Authors
  1. Sameer Bakhshi
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  2. Atul Batra
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  3. Bivas Biswas
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  4. Deepa Dhawan
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  5. Reeja Paul
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  6. Vishnubhatla Sreenivas
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Corresponding author

Correspondence to Sameer Bakhshi.

Additional information

ClinicalTrials.gov Identifier: NCT01402024

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Bakhshi, S., Batra, A., Biswas, B. et al. Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer 23, 3229–3237 (2015). https://doi.org/10.1007/s00520-015-2714-9

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  • DOI: https://doi.org/10.1007/s00520-015-2714-9

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