Combined metronomic oral therapy with Celecoxib and Cyclophosphamide for a murine mammary adenocarcinoma: antitumoral effect without cardiotoxicity

LE MAINETTI, VR ROZADOS, A ROSSA, H BERRA, MJ CISTERNA, E BURK DOS SANTOS, RD BONFIL, OG SCHAROVSKY

Los Ángeles

Congreso; 98th Annual Meeting de la American Association for Cancer Research; 2007

Multiple lines of evidence suggest that COX-2 is a promising target for cancer treatment. Many researchers have verified the relationship between COX-2 and angiogenesis. Metronomic therapy consists of a chronic, equally spaced, administration of low doses of different chemotherapeutic drugs without extended rest periods that may inhibit angiogenesis. We have previously demonstrated the antitumoral effect of Cyclophosphamide (CY) metronomic administration alone or combined with low dose of the COX-2 inhibitor Celecoxib (CEL) on the mouse mammary adenocarcinoma M-234p. To enhance the effectiveness of this type of treatment, a combination therapy using metronomic CY and higher CEL doses was assayed in another mouse mammary tumor model (M-406). CBi inbred mice were s.c. challenged on day 0 with M-406 by trocar and treated from day 8 on with: I) no treatment (controls); II) CY in the drinking water (25-30 mg/kg body weight/day); III) CEL (30 mg/kg p.o.), five times/week; IV) Treated as II + III. Tumors were measured and animals were weighted twice a week. Blood samples were taken for toxicity studies. To assess CEL-associated cardiotoxicity, EKG was performed. Mean tumor volume (± SEM, mm3) on day 22 was smaller in group IV (1138.9± 229.4) than in group I (2746.4± 493.6) (p