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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2019

01-04-2019 | Nausea | Original Article

Effect of aprepitant administration on CINV caused by cisplatin multi-day chemotherapy and pharmacokinetics of docetaxel

Authors: Lin Guo, Hao Peng, Hua-Lin Cai, Dan Tang, Hao Hu, Feng Wang, Jia Liu, Kai-Lin Que, Chen Han, Ying Zhang, Miao Yan, Jin-An Ma

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2019

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Abstract

Purpose

To compare efficacy and safety of postponing administration of aprepitant and routine triple-antiemetic treatment for chemotherapy-induced nausea and vomiting in patients who received docetaxel and cisplatin multi-day chemotherapy treatment, and to evaluate the effect of aprepitant on docetaxel pharmacokinetics in the Chinese population.

Methods

A total of 24 cancer patients (including 5 females and 19 males, 22–74 years old) received two cycles of high-emetic DP (docetaxel 75 mg/m2 on day 1 + cisplatin 25 mg/m2 on days 1–3) regimen. A randomized, two-period and cross-over study was applied for prevention of chemotherapy-induced nausea and vomiting. The patients in group A took aprepitant 125 mg on day 1 and 80 mg on days 2–3 (administered aprepitant 1 h before chemotherapy). In group B, the patients took aprepitant 125 mg on day 2, 80 mg on days 3–4, which was delayed 1 day than group A. Efficacy and safety in overall phase were evaluated within 5 days after initiation of chemotherapy. Simultaneously, the differences in the pharmacokinetic parameters of docetaxel between two different antiemetic treatments are compared.

Results

The CR rate of delayed-phase nausea was compared between the routine triple-antiemetic treatment (group A) and the aprepitant delayed 1-day administration treatment (group B), and the difference was statistically significant (16.7% vs 45.8% P < 0.05), despite there were similar for two groups in the CR rate of acute-phase nausea and vomiting, and delayed-phase vomiting. In two groups, the area under the docetaxel curve (AUC0−t values) (mean ± SD) of docetaxel was 1134.21 ± 732.55 (ng h/mL) and 1080.94 ± 585.09 (ng h/mL), and the geometric means were 944.82 and 902.10 (ng h/mL), respectively. There was no significant difference in AUC values between the two antiemetic treatments (P > 0.05), as well as Cmax, CLz, T1/2z, MRT and Tmax.

Conclusions

Delayed administration of aprepitant provided superior delayed-phase nausea protection for patients who received cisplatin-based chemotherapy in comparison with the routine triple-antiemetic treatment. In addition, in the routine triple-antiemetic treatment, aprepitant did not significantly affect the main pharmacokinetic parameters of docetaxel.
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Metadata
Title
Effect of aprepitant administration on CINV caused by cisplatin multi-day chemotherapy and pharmacokinetics of docetaxel
Authors
Lin Guo
Hao Peng
Hua-Lin Cai
Dan Tang
Hao Hu
Feng Wang
Jia Liu
Kai-Lin Que
Chen Han
Ying Zhang
Miao Yan
Jin-An Ma
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-019-03777-7

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