Combination chemotherapy with 5-fluorouracil (5FU) and 1,3-bis(2-chloro-ethyl)-1-nitrosourea (BCNU) prolongs survival of rats with dimethylhydrazine-induced colon cancer

Abstract

The effects of combination chemotherapy with 5FU and BCNU on rats with dimethylhydrazine (DMH)-induced colon cancer were investigated in a long term survival study. Eighty Wistar rats received a colon cancer producing regimen on DMH (40 mg/kg body weight/week, subcutaneously for 10 weeks). After presenting with signs of colonic disease, all rats underwent diagnostic laparotomy and colonoscopy when colon tumours were located, measured and the extent of the disease staged. Only animals with tumours (n = 63) were included and allocated to one of three tumour stages. Stage A (n = 17), had colonic tumours without serosal involvement; stage B (n = 28) had serosal involvement without metastases; stage C (n = 18) had serosal involvement with lymphadenopathy and/or metastases. Each group was randomly allocated into two subgroups, one serving as untreated controls while the other received 5FU (300 mg/m2 weekly intragastrically for life) together with BCNU (40 mg/m2 intraperitoneally on days 0, 42 and 84). The effect of chemotherapy on tumour growth was measured sequentially by colonoscopy. Animals were observed until death and necropsied, when colon carcinoma was histologically confirmed and survival analysed. The results indicate that chemotherapy significantly prolongs the survival of rats with the least advanced disease (stage A) but was of no benefit to rats with locally advanced or metastatic disease (stages B and C). Furthermore, chemotherapy was associated with a significant reduction in tumour size. Survival analyses in untreated animals show that the laparotomy staging system adopted provides accurate prognostic information. This study shows that DMH-induced colon tumours are chemosensitive, and suggests that this animal model may be a valuable testing ground for new chemotherapeutic agents.