Abstract P2-16-11: Metronomic Chemotherapy with Cyclophosphamide (CY) and Doxorubicin (DOX) Inhibits Tumor Growth and Metastases Development of Mouse Mammary Adenocarcinoma M-406
Authors: LE Mainetti, MV Fernandez Zenobi, VR Rozados, OG. Scharovsky
Journal: Cancer Research (2010)

Abstract Metronomic chemotherapy refers to the chronic, equally spaced, deliver of low doses of different chemotherapeutic drugs, without extended interruptions. We have already demonstrated that the administration, as an intervention strategy, of metronomic CY plus Celecoxib in M-406 and M-234p mammary adenocarcinomas-bearing mice, inhibited tumor growth and metastases development, increasing the survival rate. Our present aim was to study the effect of metronomic chemotherapy with CY + DOX in the M-406 tumor-model. CBi inbred mice were s.c. and i.v. challenged with M-406 cells. On day 9 (s.c.) and day 3 (i.v.), mice were distributed in four experimental groups (n=5-6/group) that received: I) Control: 0.2ml of saline i.p. 3 times/week; II) CY (20mg/kg of body weight, daily) in the drinking water; III) Dox, i.p., 0,5mg/kg, of body weight, 3 times/week; IV) Treatment II + III. Tumors were measured and body weight was determined twice a week. Blood samples were taken at the beginning and at the end of the experiments, to determine total leukocytes count. In the M-406 s.c. model, by day 19, a significant inhibition of tumor growth was evident in group II and IV with respect to control mice (P&amp;lt;0.01). Moreover, on day 41 the tumor volume of animals in group IV was significantly lower than that in group II. Also in group IV, 1 mouse over 6 showed a complete remission. The survival of mice in group IV was significantly higher than in the three other groups. In fact, on day 54, when all the animals belonging to groups I, II and III had already died, 5/6 mice in group IV were alive. In the M-406 i.v. model, animals were sacrificed on day 24 when the first mouse showed metastatic illness signs. The number of lung metastasis was significantly lower in group IV when compared to the control group (P&amp;lt;0.05). The animals in groups II and III (with single-drug treatments) showed intervening values. The total metastatic volume (Σeach metastasis volume) in groups II, III and IV was lower than that of group I (P&amp;lt;0.01), the group IV showing the lowest one. In both experiments (s.c. and i.v.) the treatment was devoid of toxicity, as evaluated by body weight evolution and, importantly, by total leukocytes count. These results clearly show that metronomic chemotherapy with a combination of cyclophosphamide and doxorubicin as an intervention strategy is able to inhibit significantly tumor growth and metastasis development in the M-406 mammary adenocarcinoma tumor-model, while being devoid of toxicity. To our knowledge, this is the first time that a metronomic schedule combining cyclophosphamide and doxorubicin is employed for the treatment of a mammary adenocarcinoma. The characteristics and the effect of the therapeutic schedule herein utilized suggest its implementation at the clinical setting in the near future. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-11.