Phase I chemoprevention study of difluoromethylornithine in subjects with organ transplants

Paul P. Carbone, John D. Pirsch, James P. Thomas, Jeffrey A. Douglas, Ajit K. Verma, Paul O. Larson, Stephen Snow, Kendra D. Tutsch, Diane Pauk

Research output: Contribution to journalArticlepeer-review


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 12-0-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.

Original languageEnglish (US)
Pages (from-to)657-661
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Issue number6
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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