Effect of aprepitant administration on CINV caused by cisplatin multi-day chemotherapy and pharmacokinetics of docetaxel
- 50 Downloads
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.
KeywordsDocetaxel 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.
- 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.Wiser W, Berger A (2005) Practical management of chemotherapy-induced nausea and vomiting. Oncology (Williston Park) 19:637–645Google Scholar
- 6.Brafford MV, Glode A (2014) Olanzapine: an antiemetic option for chemotherapy-induced nausea and vomiting. J Adv Pract Oncol 5:24–29Google Scholar
- 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
- 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.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.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.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.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.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
- 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
- 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.Zhang L (2011) Application study of aprepitant in Chinese patients with CINV. Oncol Prog 9:610–612Google Scholar
- 24.Sun JY, Miao J (2012) Correlation between antibacterial drugs and cytochrome P450. West China Med J 27:982–984Google Scholar
- 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