Abstract
BackgroundContinuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy.Design and methodsHealthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control. Blood samples were collected for analyzing biomarkers of myocardial injury and pharmacokinetics. At chosen times, sub-groups of animals were sacrificed for histopathology. A mouse breast cancer cell line (4T1), stably transfected with luciferase, was orthotopically allografted in female mice, and treated in three groups as described above for the rats. Tumor growth was monitored by measuring tumor size as well as bioluminescence.ResultsDelivery by IP bolus and by MOP achieved essentially the same area under the curve of epirubicin plasma concentration time profile. Blood biomarkers showed that the degree of myocardial injury in MOP group was lower than that of IP group. Histopathology showed that there was less eosinophilic enhancement, interstitial hemorrhage and necrotizing muscle atrophy in MOP group than IP group. In the orthotopic breast cancer allograft mouse model, the antineoplastic effect of epirubicin by MOP was not different from that by IP as measured by tumor weights or by in vivo bioluminescence.ConclusionSlow delivery of epirubicin by MOP reduced cardiotoxicity without compromising the antineoplastic effect compared to IP bolus delivery. These in vivo data support our previous clinical data that continuous intravenous infusion of epirubicin using micro infusion pumps over 48–96 hours had less cardiotoxicity than intravenous bolus injections. However, whether multiple doses of epirubicin given by MOP result in a lower magnitude of long term cardiomyopathy remains to be further investigated.
Highlights
Anthracyclines are effective antineoplastic agents against malignancies such as breast cancer, lymphoma, lung cancer, ovarian cancer, sarcomas, liver cancer, and etc
Whether multiple doses of epirubicin given by micro osmotic pumps (MOP) result in a lower magnitude of long term cardiomyopathy remains to be further investigated
We previously studied 48-hour infusion of epirubicin (70 mg/m2 in total) [14,15,16] with the goal to reduce the cardiotoxicity of epirubicin in mind, and we found that continuous intravenous infusion of epirubicin using micro-pumps had less cardiotoxicity than intravenous bolus infusion of epirubicin at the same total dose of 70 mg/m2 [14, 17]
Summary
Anthracyclines are effective antineoplastic agents against malignancies such as breast cancer, lymphoma, lung cancer, ovarian cancer, sarcomas, liver cancer, and etc. Several strategies have been used to reduce cardiotoxicity of anthracycline-based chemotherapy [4, 5]: first, by choosing anthracycline derivatives with less cardiotoxicity (e.g., epirubicin); second, by co-administration of drugs with a cardioprotective effect (e.g., dexrazoxane); third, by novel formulations of anthracyclines (e.g., PEGylated liposomal doxorubicin) [6]; and fourth, by continuous infusion [7]. Continuous infusion of epirubicin (5 mg/m2/day) for 21 days has been studied perhaps as a metronomic dosing regimen [8,9,10,11,12]. Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. Evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
