Abstract 2060: Metronomic chemotherapy (MCT): comparison of the efficacy of two combinations of drugs for the treatment of murine mammary adenocarcinomas.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Metronomic chemotherapy (MCT) refers to the chronic, equally spaced, delivery of low doses of different chemotherapeutic drugs, without extended interruptions. We have developed two combined MCT schemes for the treatment of mammary tumors: A) cyclophosphamide (Cy) 30 mg/kg/day p.o. + celecoxib (Cel) 30 mg/kg p.o. 5 times/week, and B) Cy 20 mg/kg/day p.o. + doxorubicin (Dox) 0.5 mg/kg, 3 times/week i.p. They were tested in two experimental models of mammary adenocarcinomas: I) M-406 and II) M-234p syngeneic with inbred CBi and BALB/c mice, respectively. Our present aim was to compare efficacy and toxicity of MCT combined A and B treatments in both tumor-models. There were analyzed antitumor and antimetastatic effects, survival and toxicity. The % of reduction of tumor volume of animals in the treated group with respect to control group without treatment [median (range): AI: 77.9 (50.9-89.9), AII: 84.4 (30-99.4), BI: 95.6 (57-99.6), BII: 75.5 (62.5-96.8)] didn't differ between treatments or between tumor-models (non parametric ANOVA). The % of reduction of lung metastatic burden [AI: 99.8 (97.1-99.2) AII: 99.7 (98.7-100), BI: 90.6 (35.9-96.6), BII: 90 (48.4-99.3)] was significantly different among all the groups (P<0.01); Dunn's post-test showed differences in AII vs BII (P<0.05). The analysis of survival showed higher values in treated groups, being the % of survival increase with respect to controls [AI: 56.5 (4.3-56.5) AII: 77.6 (5.3-84.2), BI: 110.9 (60-308.2), BII: 36.1 (12.4-113)] did not reach statistical significance (P=0.054). The treatments toxicity, evaluated by evolution of body weight and total leucocytes count, was similar in both tumor-models and treatments. The antitumor therapeutic efficacy was comparable in both MCT schemes and so was the toxicity generated by them. The combination Cy + Cel was superior than Cy + Dox related to antimetastatic power, suggesting its potential use at the adjuvant setting. That observation, together with the advantage that represents the oral administration of the Cy + Cel drug combination, thus leading to a better quality of life for tumor bearers, points at its election for the treatment of mammary tumors with metronomic chemotherapy. Citation Format: Maria J. Rico, Leandro E. Mainetti, Herman A. Perroud, Viviana R. Rozados, O. Graciela Scharovsky. Metronomic chemotherapy (MCT): comparison of the efficacy of two combinations of drugs for the treatment of murine mammary adenocarcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2060. doi:10.1158/1538-7445.AM2013-2060