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

• 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
• ISSN: 0250-7005; 1791-7530

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.