Increased Efficacy and Reduced Cardiotoxicity of Metronomic Treatment with Cyclophosphamide in Rat Breast Cancer

It has been reported that continuous low-dose (metronomic) administration of cytotoxic drugs may be better tolerated and may have greater antitumor effects than a single high-dose chemotherapy. The aim of this study was to examine the efficacy and cardiotoxicity of metronomic administration of two o...

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Bibliographic Details
Published in:Anticancer research 2011, Vol.31 (1), p.215-220
Main Authors: TODOROVA, Valentina K, KAUFMANN, Yihong, KLIMBERG, V. Suzanne
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - pathology
Animals
Antibiotics, Antineoplastic - administration & dosage
Antineoplastic Agents, Alkylating - administration & dosage
Biological and medical sciences
Body Weight - drug effects
Cyclophosphamide - administration & dosage
Dose-Response Relationship, Drug
Doxorubicin - administration & dosage
Echocardiography
Female
Gynecology. Andrology. Obstetrics
Heart - drug effects
Mammary gland diseases
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - pathology
Medical sciences
Rats
Rats, Inbred F344
Troponin I - blood
Tumor Cells, Cultured
Tumors
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Summary:It has been reported that continuous low-dose (metronomic) administration of cytotoxic drugs may be better tolerated and may have greater antitumor effects than a single high-dose chemotherapy. The aim of this study was to examine the efficacy and cardiotoxicity of metronomic administration of two of the most commonly used anticancer agents, cyclophosphamide (CPA) and doxorubicin (DOX), on an experimental breast cancer of rats. Breast tumors were induced in Fisher 344 female rats by implanting Mat B III cells. Rats with tumors were randomized into three groups and were treated with a total dose of 160 mg/kg CPA and a total dose of 12 mg/kg DOX, administered twice per week for four weeks. Control rats were injected with saline according to the same schedule. Echocardiography was performed before the start of treatment and before sacrifice, which took place two weeks after the last injection, when plasma troponin was also measured. The metronomic CPA eradicated the tumors and preserved body weight and echocardiographic parameters. The metronomic DOX slowed tumor growth, but was not able to prevent DOX-induced cardiotoxicity. These results suggest that the success of a metronomic chemotherapy in terms of both efficacy and toxicity depends on the target, the class and the route of administration of the anticancer agent.
ISSN:0250-7005
1791-7530