Faculty Collaboration Database

Phase I chemoprevention study of difluoromethylornithine in subjects with organ transplants. Cancer Epidemiol Biomarkers Prev 2001 Jun;10(6):657-61

Date

06/13/2001

Pubmed ID

11401916

Scopus ID

2-s2.0-0034905908 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

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.

Author List

Carbone PP, Pirsch JD, Thomas JP, Douglas JA, Verma AK, Larson PO, Snow S, Tutsch KD, Pauk D

Author

James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Agents
Chemoprevention
Eflornithine
Female
Humans
Immunosuppressive Agents
Male
Middle Aged
Organ Transplantation
Ornithine Decarboxylase
Placebos
Skin Neoplasms