Effect of 1,19-bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts.

Abstract

The polyamine analogue 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), 5 mg/kg i.p., was given twice daily on days 0-3 and 7-10 (cycle 1) to nude mice with human malignant gliomas (SF-767 and U-87 MG), lung adenocarcinoma (A549), and colon carcinomas (HCT116 and HT29). A second cycle of drug was given to mice with SF-767 and A549 tumors on days 42-45 and 49-52. The maximum animal weight loss varied between 4 and 12%, which was observed 10-15 days following the initiation of treatment, but no overt toxic reactions were noted. The SF-767 brain tumors were extremely responsive to BE-4-4-4-4 alone (3 of 8 complete regressions after 2 cycles); however, the growth of the U-87 MG brain tumor was only slightly inhibited by BE-4-4-4-4 treatment. There was significant inhibition of tumor growth after treatment with one cycle of BE-4-4-4-4 in animals carrying the A549, HCT116, and HT29 tumors. At day 73, the growth of the A549 tumor was inhibited by 78 and 89% following one or two cycles of BE-4-4-4-4, respectively. The mitotic index of A549 tumors was 18 times greater in control mice than in those treated with BE-4-4-4-4 for one or two cycles 99 days after initiation of treatment. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) was given to mice carrying the U-87 MG or A549 tumors on day 4 (cycle 1) and day 46 (cycle 2) in the maximal tolerated dose of 50 mg/kg for BCNU alone and 40 mg/kg for BCNU plus BE-4-4-4-4. BCNU alone significantly inhibited the growth of U-87 MG tumors but not the growth of A549 tumors. Treatment with the combination of BCNU and BE-4-4-4-4 was significantly better than BCNU alone for A549 tumors and better than BE-4-4-4-4 alone for U87 tumors. However, in both animal groups treated with the combination, there was a significant weight loss, which was not observed for animals treated with either agent alone. These data suggest a role for BE-4-4-4-4 in the treatment of brain, lung, and colon tumors.

• Authors: M E Dolan, M J Fleig, B G Feuerstein, H S Basu, G D Luk, R A Casero Jr, L J Marton
• Journal: Cancer research (Cancer Res) Vol. 54 Issue 17 Pg. 4698-702 (Sep 01 1994) ISSN: 0008-5472 [Print] United States
• PMID: 8062267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• BE 4-4-4-4
• Spermine
• Carmustine

Topics

• Animals
• Body Weight (drug effects)
• Brain Neoplasms (drug therapy)
• Carmustine (therapeutic use)
• Cell Division (drug effects)
• Colonic Neoplasms (drug therapy)
• Drug Screening Assays, Antitumor
• Female
• Glioblastoma (drug therapy)
• Humans
• Lung Neoplasms (drug therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Spermine (analogs & derivatives, pharmacology)
• Transplantation, Heterologous
• Tumor Cells, Cultured