Toxicity study of hepatic artery infusion chemotherapy with massive dose FUDR in rats Journal Article


Authors: Zeng, Z. S.; Zhang, Z. F.; Sigurdson, E. R.
Article Title: Toxicity study of hepatic artery infusion chemotherapy with massive dose FUDR in rats
Abstract: Hepatic artery infusion (HAI) of fluoroudeoxyuridine (FUDR) has been shown to be effective in the treatment of liver metastases from colorectal cancer. However, local toxicity is the most serious limitation of this therapy. The aetiology of HAI toxicity remains unclear. To assess the HAI toxicity, forty-eight non-tumour-bearing, healthy BD-IX rats were randomized to control or treatment groups. The control group (n = 24) received heparinized saline alone (200 u heparin kg−1 day−1) and the treatment group (n = 24) received 6.7 mg FUDR kg−1 day−1 (equivalent to the human dose of 1.0 kg−1 day−1) via HAI for 28 days. Blood samples were collected for haematologic and biochemical analysis twice a week (on days 3 and 7). Toxicity was evaluated by determination of mortality, body weight, white blood cell (WBC) count, serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and blood urea nitrogen (BUN), and creatinine. No significant differences in WBC, SGOT, BUN and creatinine levels were found between the group receiving FUDR treatment and the control group. Significantly higher total bilirubin levels, mortality and body weight loss were found in the FUDR-treated group than in the control group. A multivariate analysis revealed that total bilirubin level was the only significant predictor of mortality in the FUDR treatment group. These results suggested that biliary tract damage seems to be the principal toxicity of HAI FUDR chemotherapy. © 1995, Blackwell Science Ltd.. All rights reserved.
Keywords: controlled study; mortality; diarrhea; nonhuman; colorectal cancer; animal experiment; animal model; body weight; weight reduction; creatinine; urea nitrogen blood level; aspartate aminotransferase blood level; alkaline phosphatase; aspartate aminotransferase; bilirubin; liver metastasis; blood sampling; rat; intraarterial drug administration; multivariate analysis; alkaline phosphatase blood level; leukocyte count; toxicity; floxuridine; biochemistry; hepatic artery; hematology; liver metastases; urea; bile duct injury; hepatic artery infusion; fudr; priority journal; article
Journal Title: Surgical Oncology
Volume: 4
Issue: 3
ISSN: 0960-7404
Publisher: Elsevier Inc.  
Date Published: 1995-06-01
Start Page: 147
End Page: 155
Language: English
DOI: 10.1016/s0960-7404(10)80019-2
PUBMED: 7582187
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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  1. Zhaoshi Zeng
    87 Zeng
  2. Zuo-Feng Zhang
    102 Zhang