Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on Human Tumor Xenografts

M. Eileen Dolan, Matthew J. Fleig, Burt G. Feuerstein, Hirak S. Basu, Gordon D. Luk, Robert A. Casero, Laurence J. Marton

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30 Scopus citations

Abstract

The polyamine analogue l,19-bis(ethylamino)-5,10,15-triazanonade-cane (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 l,3-Bis(2-cMoroethyI)-l-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.

Original languageEnglish (US)
Pages (from-to)4698-4702
Number of pages5
JournalCancer Research
Volume54
Issue number17
StatePublished - Sep 1994
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Dolan, M. E., Fleig, M. J., Feuerstein, B. G., Basu, H. S., Luk, G. D., Casero, R. A., & Marton, L. J. (1994). Effect of 1,19-Bis(ethylamino)-5,10,15-triazanonadecane on Human Tumor Xenografts. Cancer Research, 54(17), 4698-4702.