Study on the infusion‑site adverse events and vascular distribution of epirubicin in chemotherapy with epirubicin and fosaprepitant

Yamasaki,Miho; Kimura,Ryuji; Mayahara,Shigeri; Maeda,Yorinobu; Takahashi,Mamoru; Nishida,Toshihiro; Oda,Keisuke; Murakami,Teruo

doi:10.3892/mco.2019.1849

Study on the infusion‑site adverse events and vascular distribution of epirubicin in chemotherapy with epirubicin and fosaprepitant

Authors:
- Miho Yamasaki
- Ryuji Kimura
- Shigeri Mayahara
- Yorinobu Maeda
- Mamoru Takahashi
- Toshihiro Nishida
- Keisuke Oda
- Teruo Murakami
View Affiliations

Affiliations: Department of Pharmacy, Chugoku Rosai Hospital, Kure, Hiroshima 737‑0193, Japan, Department of Breast Surgery, Chugoku Rosai Hospital, Kure, Hiroshima 737‑0193, Japan, Department of Diagnostic Pathology, Chugoku Rosai Hospital, Kure, Hiroshima 737‑0193, Japan, Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Hiroshima 737‑0112, Japan
Published online on: April 24, 2019 https://doi.org/10.3892/mco.2019.1849
Pages: 43-49
Copyright: © Yamasaki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In breast cancer patients on a fluorouracil‑epirubicin (EPI)‑cyclophosphamide (FEC) regimen and intravenous fosaprepitant (FAP) during chemotherapy, infusion‑site adverse events such as vascular pain and induration and/or phlebitis are observed. In the present study, adverse events induced by the FEC regimen and FAP, a prodrug of aprepitant (AP), were studied based on the vascular tissue distribution of EPI in rats. Rats were treated with intravenous FAP (3 mg/kg, 10 min‑constant rate infusion) or oral AP (3 mg/kg) and then intravenous EPI (1 mg/kg, 5 min‑constant rate infusion) as follows: FAP‑S Group, FAP and then EPI was infused from the same site on the jugular vein; FAP‑D Group, FAP and then EPI was infused from different jugular veins (left and right); and AP Group, AP was administered orally and EPI was infused from the jugular vein. Concentrations of EPI in vascular tissue at the EPI infusion sites and opposite sites of the jugular vein (left and right, respectively) were measured at 30 min and 24 h after EPI infusion. Histological observation of the EPI infusion site was also made separately. In rats, the tissue concentrations of EPI at the infusion site in the FAP‑S group were higher than those in the FAP‑D and AP groups. Inflammation and necrosis were observed at the EPI infusion‑site vascular tissue of the FAP‑S group, but not of the FAP‑D and AP groups. These findings could aid the development of an approach to avoid infusion‑site adverse events in anthracycline‑based chemotherapy in the clinical practice.

View Figures

View References

1	Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis L, Dusetzina SB, et al: Antiemetics: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 35:3240–3261. 2017. View Article : Google Scholar : PubMed/NCBI
2	Rolia F, Molassiotis A, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, et al: 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 27 (Suppl 5):v119–v133. 2016. View Article : Google Scholar : PubMed/NCBI
3	Berger MJ, Ettinger DS, Aston J, Barbour S, Bergsbaken J, Bierman PJ, Brandt D, Dolan DE, Ellis G, Kim EJ, et al: NCCN guidelines insights: Antiemesis, version 2.2017. J Natl Compr Canc Netw. 15:883–893. 2017. View Article : Google Scholar : PubMed/NCBI
4	Pritchett W and Kinsley K: Benefits and risks of fosaprepitant in patients receiving emetogenic regimens. Clin J Oncol Nurs. 20:555–556. 2016. View Article : Google Scholar : PubMed/NCBI
5	Chow AY, Chin C, Dahl G and Rosenthal DN: Anthracyclines cause endothelial injury in pediatric cancer patients: A pilot study. J Clin Oncol. 24:925–928. 2006. View Article : Google Scholar : PubMed/NCBI
6	Ben Aharon I, Bar Joseph H, Tzabari M, Shenkman B, Farzam N, Levi M, Shalgi R, Stemmer SM and Savion N: Doxorubicin-induced vascular toxicity-targeting potential pathways may reduce procoagulant activity. PLoS One. 8:e751572013. View Article : Google Scholar : PubMed/NCBI
7	Bar-Joseph H, Stemmer SM, Tsarfaty I, Shalgi R and Ben-Aharon I: Chemotherapy-induced vascular toxicity-real-time in vivo imaging of vessel impairment. J Vis Exp. e516502015.PubMed/NCBI
8	Lundberg JD, Crawford BS, Phillips G, Berger MJ and Wesolowski R: Incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant. Support Care Cancer. 22:1461–1466. 2014. View Article : Google Scholar : PubMed/NCBI
9	Chau E, Lundberg J, Phillips G, Berger M and Wesolowski R: Updated report on incidence of infusion-site reactions associated with peripheral intravenous administration of fosaprepitant. J Oncol Pharm Pract. 10781552187693472018.PubMed/NCBI
10	Sato Y, Kondo M, Inagaki A, Komatsu H, Okada C, Naruse K, Sahashi T, Kuroda J, Ogura H, Uegaki S, et al: Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients. J Cancer. 5:390–397. 2014. View Article : Google Scholar : PubMed/NCBI
11	Lead AD, Kadakia KC, Looker S, Hilger C, Sorgatz K, Anderson K, Jacobson A, Grendahl D, Seisler D, Hobday T and Loprinzi CL: Fosaprepitant-induced phlebitis: A focus on patients receiving doxorubicin/cyclophosphamide therapy. Support Care Cancer. 22:1313–1317. 2014. View Article : Google Scholar : PubMed/NCBI
12	Patel P, Leeder JS, Piquette-Miller M and Dupuis LL: Aprepitant and fosaprepitant drug interactions: A systematic review. Br J Clin Pharmacol. 83:2148–2162. 2017. View Article : Google Scholar : PubMed/NCBI
13	Mauri D, Pavlidis N and Ioannidis JPA: Neoadjuvant versus adjuvant systemic treatment in breast cancer: A meta-analysis. J Natl Cancer Inst. 97:188–194. 2005. View Article : Google Scholar : PubMed/NCBI
14	Tsuda T, Kyomori C, Mizukami T, Taniyama T, Izawa N, Horie Y, Hirakawa M, Ogura T, Nakajima T, Tsugawa K and Boku N: Infusion site adverse events in breast cancer patients receiving highly emetic chemotherapy with prophylactic anti-emetic treatment with aprepitant and fosaprepitant: A retrospective comparison. Mol Clin Oncol. 4:603–606. 2016. View Article : Google Scholar : PubMed/NCBI
15	Fujii T, Nishimura N, Urayama KY, Kanai H, Ishimaru H, Kawano J, Takahashi O, Yamauchi H and Yamauchi T: Differential impact of fosaprepitant on infusion site adverse events between cisplatin- and anthracycline-based chemotherapy regimens. Anticancer Res. 35:379–383. 2015.PubMed/NCBI
16	Italia C, Paglia L, Trabattoni A, Luchini S, Villas F, Beretta L, Marelli G and Natale N: Distribution of 4′Epi-doxorubicin in human tissues. Br J Cancer. 47:545–547. 1983. View Article : Google Scholar : PubMed/NCBI
17	Camaggi CM, Strocchi E, Carisi P, Martoni A, Melotti B and Pannuti F: Epirubicin metabolism and pharmacokinetics after conventional- and high-dose intravenous administration: A cross-over study. Cancer Chemother Pharmacol. 32:301–309. 1993. View Article : Google Scholar : PubMed/NCBI
18	Robert J: Clinical pharmacokinetics of epirubicin. Clin Pharmacokinet. 26:428–438. 1994. View Article : Google Scholar : PubMed/NCBI
19	Chen R, Li J, Hu WW, Wang ML, Zou SL and Miao LY: Circadian variability of pharmacokinetics of cisplatin in patients with non-small-cell lung carcinoma: Analysis with the NONMEM program. Cancer Chemother Pharmacol. 72:1111–1123. 2013. View Article : Google Scholar : PubMed/NCBI
20	Murakami T and Yumoto R: Role of phosphatidylserine binding in tissue distribution of amine-containing basic compounds. Expert Opin Drug Metab Toxicol. 7:353–364. 2011. View Article : Google Scholar : PubMed/NCBI
21	Interview Form ‘PROEMEND for intravenous infusion 150 mg’. March. 2016, http://www.pmda.go.jp/
22	Ottoboni T, Keller MR, Cravets M, Clendeninn N and Quart B: Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: A phase I, open-label, randomized, two-way crossover evaluation. Drug Des Devel Ther. 12:429–435. 2018. View Article : Google Scholar : PubMed/NCBI
23	Ottoboni T, Lauw M, Keller MR, Cravets M, Manhard K, Clendeninn N and Quart B: Safety of HTX-019 (intravenous aprepitant) and fosaprepitant in healthy subjects. Future Oncol. 14:2849–2859. 2018. View Article : Google Scholar : PubMed/NCBI
24	Schwartzberg LS and Navari RM: Safety of polysorbate 80 in the oncology setting. Adv Ther. 35:754–767. 2018. View Article : Google Scholar : PubMed/NCBI