An experimental study of continuous low-dose chemotherapy with cetuximab on colon carcinoma / 中华普通外科杂志

ABSTRACT

objectlve To investigate the efficacy of continuous low-dose fluorouracil with cetuximab for antiangiogenic effect on colon carcinoma xenograft,and test its antitumor effect and toxicity.Methods Balb/c mice bearing CT-26 colon carcinoma xenograft were randomly divided into five groups,receiving low-dose metronomic(LDM)fluorouracil,maximum tolerated dose(MTD)fluorouracil,cetuximab,LDM fluorouracil with cetuximab therapy and saline respectively.Tumor growth,weight loss,peripheral white blood cell counts and survival of mice were monitoted.At the end of experiment,tumors were resected for tumor microvascular density(MVD)by immunofluorescence staining. Results Tumor growth inhibition was found in mice receiving LDM fluorouracil therapy and combined therapy,without significant body weight loss or leukopenia,and the survival of mice was remarkably prolonged,compared with mice receiving MTD fluorouracil or cetuximab therapy,and the antitumor effects of the combined therapy was stronger than that of the fluorouracil LDM therapy.LDM treatment and combine treatment led to statistically significant(P＜0.05)55%and 71%reduction in tumor growth,as well as 73%and 77% reduction in tumor microvessel density compared with the control respectively.Additonally,tunnel staining shows no significant difference between these treatment groups. Conclusion Continuous low-dose regimen of fluorouracil with cetuximab can significantly increase the therapeutic activity with decreased toxicity and prolonged animal survival bearing implanted colon cancer.