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



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.


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.


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.


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.


Docetaxel Aprepitant DP chemotherapy CINV Pharmacokinetic 



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.


  1. 1.
    Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358:2482–2494CrossRefGoogle Scholar
  2. 2.
    Yuan DM, Li Q, Zhang Q, Xiao XW, Yao YW, Zhang Y, Lv YL, Liu HB, Lv TF, Song Y (2016) Efficacy and Safety of neurokinin-1 receptor antagonists for prevention of chemotherapy-induced nausea and vomiting: systematic review and meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev 17:1661–1675CrossRefGoogle Scholar
  3. 3.
    Wiser W, Berger A (2005) Practical management of chemotherapy-induced nausea and vomiting. Oncology (Williston Park) 19:637–645Google Scholar
  4. 4.
    Trigg ME, Higa GM (2010) Chemotherapy-induced nausea and vomiting: antiemetic trials that impacted clinical practice. J Oncol Pharm Pract 16:233–244CrossRefGoogle Scholar
  5. 5.
    Rojas C, Slusher BS (2015) Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: rolapitant and NEPA (netupitant/palonosetron). Cancer Treat Rev 41:904–913CrossRefGoogle Scholar
  6. 6.
    Brafford MV, Glode A (2014) Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting. J Adv Pract Oncol 5:24–29Google Scholar
  7. 7.
    Berger MJ, Ettinger DS, Aston J, Barbour S, Bergsbaken J, Bierman PJ, Brandt D, Dolan DE, Ellis G, Kim EJ et al (2017) NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw 15:883–893CrossRefGoogle Scholar
  8. 8.
    (2016) Erratum: Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy. Cancer-Am Cancer Soc 122: 3579Google Scholar
  9. 9.
    Roila F, Donati D, Tamberi S, Margutti G (2002) Delayed emesis: incidence, pattern, prognostic factors and optimal treatment. Support Care Cancer 10:88–95CrossRefGoogle Scholar
  10. 10.
    Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Schmidt C, Taylor A, Carides AD, Evans JK, Horgan KJ (2003) Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer-Am Cancer Soc 97:2290–2300Google Scholar
  11. 11.
    Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH (2012) Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol 30:3998–4003CrossRefGoogle Scholar
  12. 12.
    Uchida M, Ikesue H, Kato K, Ichinose K, Hiraiwa H, Sakurai A, Takenaka K, Iwasaki H, Miyamoto T, Teshima T, Egashira N, Akashi K, Oishi R (2013) Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy. Am J Health Syst Pharm 70:343–349CrossRefGoogle Scholar
  13. 13.
    Olver IN, Grimison P, Chatfield M, Stockler MR, Toner GC, Gebski V, Harrup R, Underhill C, Kichenadasse G, Singhal N, Davis ID, Boland A, McDonald A, Thomson D (2013) Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy. Support Care Cancer 21:1561–1568CrossRefGoogle Scholar
  14. 14.
    Yu SY, Yin JL, Qin SK, Wang JJ, Chen Y, Shen L, Xu JG, Xu GR, Zhang L et al (2014) Guidelines for the treatment of vomiting related to cancer treatment (Version 2014). J Clin Oncol 19:263–273Google Scholar
  15. 15.
    Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach RS, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA (2003) The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos 31:815–832CrossRefGoogle Scholar
  16. 16.
    Majumdar AK, McCrea JB, Panebianco DL, Hesney M, Dru J, Constanzer M, Goldberg MR, Murphy G, Gottesdiener KM, Lines CR, Petty KJ, Blum RA (2003) Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clin Pharmacol Ther 74:150–156CrossRefGoogle Scholar
  17. 17.
    Kaneta T, Fujita K, Akiyama Y, Kawara K, Sunakawa Y, Kawachi A, Shimada K, Sasaki Y (2014) No pharmacokinetic alteration of docetaxel following coadministration of aprepitant 3 h before docetaxel infusion. Cancer Chemother Pharmacol 74:539–547CrossRefGoogle Scholar
  18. 18.
    Nygren P, Hande K, Petty KJ, Fedgchin M, van Dyck K, Majumdar A, Panebianco D, de Smet M, Ahmed T, Murphy MG, Gottesdiener KM, Cocquyt V, van Belle S (2005) Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol 55:609–616CrossRefGoogle Scholar
  19. 19.
    Langaee TY, Gong Y, Yarandi HN, Katz DA, Cooper-DeHoff RM, Pepine CJ, Johnson JA (2007) Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. Clin Pharmacol Ther 81:386–391CrossRefGoogle Scholar
  20. 20.
    Kudzi W, Dodoo AN, Mills JJ (2010) Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans? Bmc Med Genet 11:111CrossRefGoogle Scholar
  21. 21.
    Sekine I, Segawa Y, Kubota K, Saeki T (2013) Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci 104:711–717CrossRefGoogle Scholar
  22. 22.
    Gralla RJ, de Wit R, Herrstedt J, Carides AD, Ianus J, Guoguang-Ma J, Evans JK, Horgan KJ (2005) Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials. Cancer Am Cancer Soc 104:864–868Google Scholar
  23. 23.
    Zhang L (2011) Application study of aprepitant in Chinese patients with CINV. Oncol Prog 9:610–612Google Scholar
  24. 24.
    Sun JY, Miao J (2012) Correlation between antibacterial drugs and cytochrome P450. West China Med J 27:982–984Google Scholar
  25. 25.
    Wang F, Cheng Z, Li L, Zhu MZ, Xiong YY, Gu YT (2016) Pharmacokinetically determined docetaxel exposure as a predictor of hematologic toxicity in Chinese patients with early stage breast cancer. J Chin Pharm Sci 25:512–516Google Scholar
  26. 26.
    Rudek MA, Sparreboom A, Garrett-Mayer ES, Armstrong DK, Wolff AC, Verweij J, Baker SD (2004) Factors affecting pharmacokinetic variability following doxorubicin and docetaxel-based therapy. Eur J Cancer 40:1170–1178CrossRefGoogle Scholar
  27. 27.
    Andriguetti NB, Raymundo S, Antunes MV, Perassolo MS, Verza SG, Suyenaga ES, Linden R (2017) Pharmacogenetic and pharmacokinetic dose individualization of the taxane chemotherapeutic drugs paclitaxel and docetaxel. Curr Med Chem 24:3559–3582CrossRefGoogle Scholar
  28. 28.
    Engels FK, Loos WJ, van der Bol JM, de Bruijn P, Mathijssen RH, Verweij J, Mathot RA (2011) Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study. Clin Cancer Res 17:353–362CrossRefGoogle Scholar

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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