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Efficacy, Tolerability and Pharmacokinetic Impact of Aprepitant in Sarcoma Patients Receiving Ifosfamide and Doxorubicin Chemotherapy: A Randomized Controlled Trial

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Aprepitant, a selective neurokinin-1 receptor antagonist approved for prevention of chemotherapy-induced nausea and vomiting (CINV), is an inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme, which is involved in the clearance of several chemotherapeutic agents. Here we evaluated the efficacy and toxicity of a combination of aprepitant, palonosetron, and dexamethasone as antiemetic prophylaxis in sarcoma patients receiving ifosfamide and doxorubicin chemotherapy, and examined the potential of aprepitant to affect the pharmacokinetics of ifosfamide, which is primarily metabolized by CYP3A4.


A total of 108 sarcoma patients were randomly assigned to either the aprepitant group (antiemetic regimen: aprepitant, palonosetron, and dexamethasone) or the control group (antiemetic regimen: palonosetron and dexamethasone). Data on nausea, vomiting, and use of rescue medication were collected, and the primary efficacy end point was the proportion of patients with complete response (CR), defined as no vomiting and no use of rescue therapy during 120 h after initiation of chemotherapy. Tolerability was evaluated on the basis of reported adverse events and laboratory assessments. Blood samples for ifosfamide pharmacokinetic analysis were collected in ten patients.


The percentage of patients achieving CR was significantly higher in the aprepitant group compared with that in the control group in the acute, delay, and overall phase (78.4% vs. 59.3%, 74.5% vs. 48.1%, and 68.6% vs. 37.0%, p < 0.05, respectively). No significant differences of adverse events or hematological toxicity were detected between the two groups. Concomitant administration of aprepitant did not cause any statistically significant changes in ifosfamide pharmacokinetics. Values for aprepitant group vs. control group were as follows: geometric mean of Cmax was 119 vs. 120 ng/mL, AUC0–last was 648 vs. 635 ng h/mL, AUC0–inf was 681 vs. 668 ng h/mL, plasma clearance was 4.40 vs. 4.49 (L/h/m2), respectively; harmonic means of t1/2 was 2.11 vs. 2.25 h.


This study showed that aprepitant in combination with palonosetron and dexamethasone was safe and effectively controlled CINV in sarcoma patients receiving ifosfamide and doxorubicin chemotherapy. Aprepitant may have a low potential to affect the pharmacokinetics of chemotherapeutic agents metabolized by CYP3A4.

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The authors would like to thank the patients who participated in this study.


Sponsorship for this study and article processing charges were funded by the Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

Medical Writing Assistance

Medical writing assistance was provided by Fang Xiefan, PhD, from Charles River Laboratories, INC. 6995 Longley Lane, Reno, NV 89511, USA. No funding was received for this assistance.


All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.


Xiong Jie, Zhao Guifang, Yang Shengli, and Chen Jing declare that they have no conflict of interest.

Compliance with Ethics Guidelines

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Data Availability

The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Jing Chen.

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Xiong, J., Zhao, G., Yang, S. et al. Efficacy, Tolerability and Pharmacokinetic Impact of Aprepitant in Sarcoma Patients Receiving Ifosfamide and Doxorubicin Chemotherapy: A Randomized Controlled Trial. Adv Ther 36, 355–364 (2019).

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