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

  • Lin Guo
  • Hao Peng
  • Hua-Lin Cai
  • Dan Tang
  • Hao Hu
  • Feng Wang
  • Jia Liu
  • Kai-Lin Que
  • Chen Han
  • Ying Zhang
  • Miao YanEmail author
  • Jin-An MaEmail author
Original Article
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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.

Keywords

Docetaxel Aprepitant DP chemotherapy CINV Pharmacokinetic 

Notes

Acknowledgements

We are very grateful to the volunteers and nurses who support the clinical research work.

Compliance with ethical standards

Conflict of interest

There is no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lin Guo
    • 1
  • Hao Peng
    • 2
  • Hua-Lin Cai
    • 1
  • Dan Tang
    • 1
  • Hao Hu
    • 2
  • Feng Wang
    • 1
  • Jia Liu
    • 2
  • Kai-Lin Que
    • 2
  • Chen Han
    • 2
  • Ying Zhang
    • 2
  • Miao Yan
    • 1
    • 3
    Email author
  • Jin-An Ma
    • 2
    Email author
  1. 1.Department of Pharmacy, The Second Xiangya HospitalCentral South UniversityChangshaChina
  2. 2.Department of Oncology, The Second Xiangya HospitalCentral South UniversityChangshaChina
  3. 3.Institute of Clinical PharmacyCentral South UniversityChangshaChina

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