Antitumoral and antimetastatic effects of metronomic chemotherapy with cyclophosphamide combined with celecoxib on murine mammary adenocarcinomas

Abstract

Purpose Metronomic chemotherapy (MCT) refers to thechronic and equally spaced administration of low doses ofdifferent chemotherapy drugs, without extended interruptions.Previously, we demonstrated the antitumor effect ofMCT with cyclophosphamide (Cy) in a mouse mammaryadenocarcinoma model. Herein, we investigated the therapeuticefficacy of metronomic Cy combined with celecoxib(Cel) in two murine mammary adenocarcinomamodels.Methods Mice were s.c. challenged with M-234p orM-406 mammary tumors and from day 5 or 8 on, respectively,treated with: (I) no treatment (controls); (II) Cy inthe drinking water (25?30 mg/kg body weight/day); (III)Cel (30 mg/kg p.o.), five times/week; (IV) treated asII ? III. Mice challenged i.v. with M-234p or M-406tumor cells received, on day 3, the same treatments.Results We found that MCT with Cy plus Cel inhibitedtumor growth decreased lung metastases, and increased themedian survival time, in both tumor models, having verylow toxicity. MCT with Cy combined with Cel was moreeffective than each monotherapy.