BACKGROUNDRecently a number of preclinical studies have sparked interest in the concept of exploiting conventional chemotherapeutic drugs as antiangiogenics. Such antiangiogenic activity is achieved by metronomic-dosing (low-dose) protocols. This new target may have some advantages in avoiding toxicity and resistance caused by chemotherapeutic drugs. This study is to test the efficacy of continuous low-dose cyclophosphamide (CTX) for antiangiogenic effect on Lewis lung carcinoma, and investigate its antitumor effect and toxicity.

METHODSC57/BL6 mice bearing Lewis lung carcinoma were randomly divided into three groups, receiving low-dose metronomic (LDM) CTX, maximum tolerated dose (MTD) CTX therapy and saline respectively. Tumor growth, weight loss, peripheral white blood cell counts and survival of mice were monitored in each group. At the end of experiment, tumors were resected for immunohistochemical staining. Tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) level were detected by immunohistochemical staining.

RESULTSMVD and VEGF expression of tumors were much lower in the mice received LDM CTX therapy than those in control group and MTD CTX group (P < 0.05). During the experiment, growth delays of tumor were found in the mice received LDM CTX therapy, without apparent body weight loss or leukopenia, and the survival of mice was remarkably prolonged, compared with mice received MTD CTX therapy (P < 0.05).

CONCLUSIONSThe continuous low-dose regimen of CTX can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival for lung cancer. It may act as an antiangiogenic and lead to less drug resistance.