Pharmacokinetic and Myocardial Enzyme Profiles of Two Administration Routes of Epirubicin in Breast Cancer Patients
received 30 June 2012
accepted 31 October 2012
30 November 2012 (eFirst)
To evaluate the changes in myocardial enzymes and plasma epirubicin concentration following administration by micro-pump (MP) and intravenous drip (ID) in breast cancer patients.
11 self-controlled breast cancer patients were recruited for a trial with epirubicin administration by MP for 48 h and by ID for 1 h during 2 cycles of treatment. Plasma concentration of epirubicin at different time points was determined using LC-MS/MS. The levels of myocardial enzymes before and after chemotherapy were compared. Another group of patients receiving epirubicin by ID (n=4) or MP (n=9) were monitored for 4 months.
8 patients completed the self-controlled study. The peak concentration of epirubicin in the MP group and the ID group were 21.84±18.85 ng/mL and 294.80±225.54 ng/mL, respectively. The MP group had a longer duration (54~60 h) of plasma concentration of epirubicin not less than 10 ng/mL than that of the ID group (8~14 h). There was significant difference for the alteration of myocardial enzymes before and after chemotherapy (p<0.05) in the ID group, whereas the MP group showed no significant difference (p>0.05). The increased range of myocardial enzymes after chemotherapy in the ID group was larger than that of the MP group and the difference was significant (p<0.05). There is an increased cardiotoxicity in patients receiving epirubicin by ID during the 4-month trial.
Administration of epirubicin by MP maintained an effective drug concentration for a longer period of time than by ID. The higher peak plasma concentration observed following epirubicin administration by ID may lead to cardiac toxicity.
- 1 Khasraw M, Bell R, Dang C. Epirubicin: is it like doxorubicin in breast cancer? A clinical review. Breast 2012; 21: 142-149
- 2 Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003; 97: 2869-2879
- 3 Yang RX, Ren HX, Zhuang L et al. Toxic side effects of micro-pump and intravenous drip of Epirubicin. Cancer Res Prev Treat 2009; 36: 872-875 (in Chinese)
- 4 Chapelle JP. Cardiac troponin I and troponin T: recent players in the field of myocardial markers. Clin Chem Lab Med 1999; 37: 11-20
- 5 Gianni L, Munzone E, Capri G et al. Paclitaxel by 3 hour infusion with bolus doxorubincin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. Clin Oncol 1995; 13: 2688-2699
- 6 Zhang YQ, Ge YQ, Wang HY. Comparison of pharmacokinetics of pirarubicin and epirubicin after continuous infusion through ear vein and internal iliac artery of rabbits. Shanghai Med J 2008; 31: 873-876 (in Chinese)
- 7 Wu CF, Chen CM, Chen CH et al. Continuous intraarterial infusion chemotherapy for early lip cancer. Oral Oncol 2007; 43: 825-830
- 8 Iguchi H, Kuboki H, Hirano H et al. Intra-arterial hepatic chemotherapy with pirarubicin: Pharmacokinetics in rabbits and dogs. Reg Cancer Treat 1992; 1: 6-11
- 9 Tan H, Yang RX, Luo CX et al. Comparative study on QTVI based evaluating of toxicity and side effects of Epirubicin to heart from micropump and from intravenous drip medication. Cancer Res Prev Treat 2010; 37: 342-345 (in Chinese)
- 10 Casazza AM, Ciuliani FC. Preclinical properties of epirubicin. in Bonadonna G. (ed.). Advance in anthracycline chemotherapy: Epirubicin. Milano: Masson; 1984: 31-40
- 11 Wang JY, Xu BH, Sun Y. The clinical analysis of Ifosfamide and Epirubicin treatment of advanced soft tissue sarcoma in 27 cases. Chin J Clin Oncol Rehabil 2009; 16: 51-53 (in Chinese)