[Antitumor activity and metabolism of BOF-A2, a new 5-fluorouracil derivative, with human cancers xenografted in nude mice]

• Abstract: Antitumor activity of BOF-A2, a new 5-fluorouracil (5-FU) derivative, was evaluated with human gastric (H-111 and H-81), colorectal (H-143), pancreatic (H-48) and breast (H-31) cancers xenografted in nude mice. Twenty-five consecutive oral administration of BOF-A2 at 17.5 to 30 mg/kg over 4 weeks caused marked inhibition or regression (over 92% of inhibition rate) to the growth of H-81, H-143 and H-31 cancers. Moreover, BOF-A2 effected to both H-111 and H-48 which have low sensitivity to 5-FU and its known derivatives. Throughout the experiments, the mice seemed to tolerate the consecutive administration of BOF-A2 without severe toxicity. When BOF-A2 was given orally, 5-FU levels in the blood of mice was notably durative for a long time as compared to 5-FU and UFT. Furthermore, 5-FU levels in the tumor tissue tended to increase and persist much more than those in the blood. This maintenance and persistence of objective level of 5-FU in the blood would be concluded to produce a high antitumor effect of BOF-A2 against human cancers xenografted in nude mice.
• Authors: T Shirasaka, F Fujita, M Fujita, M Fukushima, T Taguchi, S Fujii (Affiliation: Biwako Research Institute, Otsuka Pharmaceutical Co., Ltd.)
• Journal: Gan to kagaku ryoho. Cancer & chemotherapy (Gan To Kagaku Ryoho) Vol. 17 Issue 9 Pg. 1871-6 (Sep 1990) ISSN: 0385-0684 [Print] JAPAN
• PMID: 2393305 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antineoplastic Agents
• Emitefur
• Fluorouracil

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Fluorouracil (analogs & derivatives, pharmacokinetics, therapeutic use)
• Humans
• Liver (metabolism)
• Mice
• Mice, Nude
• Microsomes (metabolism)
• Neoplasm Transplantation
• Neoplasms, Experimental (drug therapy, metabolism, pathology)
• Pancreatic Neoplasms (drug therapy, pathology)
• Stomach Neoplasms (drug therapy, pathology)