Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water.

摘要: A number of recent preclinical studies have sparked interest in the conceptof exploiting conventional chemotherapeutic drugs as antiangiogenics. Such antiangiogenic activity is achieved or optimized by metronomic-dosing protocols which drug given at comparatively low doses using a frequent schedule administration ( e.g. , once to three times per week) with no breaks, particularly when combined an endothelial cell-specific drug. The use p.o. suitable for this type treatment strategy. We tested one such drug, cyclophosphamide (CTX), protocol wherein was administered mice doses, ∼10–40 mg/kg on daily basis through drinking water. CTX typically patients, but it has almost always been injected treating mouse tumor models. found be safe and convenient significant antitumor efficacy. Growth delays were observed human orthotopic breast ectopic colon cancer xenografts nude SCID mice. Established PC3 prostate could induced fully regress, remaining virtually nonpalpable ≥2 months continuous therapy, after tumors began grow progressively. These re-emergent not resistant new hosts, same protocol. Regression spontaneously arising, late-stage pancreatic islet cell carcinomas Rip Tag transgenic also observed. effects enhanced significantly orthotopic, metastatic xenograft model used combination antivascular growth factor receptor-2 blocking antibody. Maximum tolerated dose levels established other strains proved highly toxic mice, whereas low-dose regimens well tolerated. Taken together, results demonstrate feasibility delivering metronomic chemotherapy regimen, safe, reasonably efficacious, potentially applicable chronic treatment. regimen may suited integration drugs.