This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carbone, P. P. Articles by Pauk, D. Search for Related Content PubMed PubMed Citation Articles by Carbone, P. P. Articles by Pauk, D.

Phase I Chemoprevention Study of Difluoromethylornithine in Subjects with Organ Transplants¹

University of Wisconsin Comprehensive Cancer Center [P. P. C., J. P. T., J. A. D., A. K. V., P. O. L., K. D. T., D. P.] and Departments of Medicine [P. P. C., J. P. T.], Human Oncology [A. K. V.], Biostatistics and Informatics [J. A. D.], and Surgery [J. D. P., P. O. L., S. S.], University of Wisconsin Medical School, Madison, Wisconsin 53792

Individuals who receive life-saving organ transplants and the required immunosuppression often develop secondary cancers. One of the most common secondary cancers is nonmelanoma skin cancer in sun-exposed areas. Attempts to prevent these cancers have not been successful. Difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), is a known experimental cancer prevention agent that is being evaluated in a number of human cancer prevention trials. This report describes a Phase I trial in 18 organ transplant recipients, randomized to 1.0 and 0.5 g of DFMO or a placebo, designed to look at short-term toxicities over 28 days as well as the impact of DFMO on two biological parameters, skin polyamines and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity. Blood levels of DFMO were also measured. The results indicate that DFMO was well tolerated over the 28-day period. The TPA-induced ODC activity in 3-mm skin biopsies was significantly lowered by 80 and 67% at the two dose levels. Polyamine levels were not affected significantly except for putrescine at the 0.5-g level. Blood levels of DFMO were about two times higher than expected, based on our prior pharmacokinetic studies. Our studies indicate that DFMO is a reasonable agent that should be tested further in larger Phase 2b trials in this population as a chemopreventive agent. TPA-induced ODC activity appears to be a relevant intermediate biological assay.

This article has been cited by other articles:

				A.-T. Vlastos, L. A. West, E. N. Atkinson, I. Boiko, A. Malpica, W. K. Hong, and M. Follen Results of a Phase II Double-Blinded Randomized Clinical Trial of Difluoromethylornithine for Cervical Intraepithelial Neoplasia Grades 2 to 3 Clin. Cancer Res., January 1, 2005; 11(1): 390 - 396. [Abstract] [Full Text] [PDF]

				L. Y. Y. Fong, D. J. Feith, and A. E. Pegg Antizyme Overexpression in Transgenic Mice Reduces Cell Proliferation, Increases Apoptosis, and Reduces N-Nitrosomethylbenzylamine-induced Forestomach Carcinogenesis Cancer Res., July 15, 2003; 63(14): 3945 - 3954. [Abstract] [Full Text] [PDF]

				C. J. Fabian, B. F. Kimler, D. A. Brady, M. S. Mayo, C. H. J. Chang, J. A. Ferraro, C. M. Zalles, A. L. Stanton, S. Masood, W. E. Grizzle, et al. A Phase II Breast Cancer Chemoprevention Trial of Oral {alpha}-Difluoromethylornithine: Breast Tissue, Imaging, and Serum and Urine Biomarkers Clin. Cancer Res., October 1, 2002; 8(10): 3105 - 3117. [Abstract] [Full Text] [PDF]