Chemopreventive efficacy of topical difluoromethylornithine and/or triamcinolone in the treatment of actinic keratoses analyzed by karyometry.
OBJECTIVE
To determine whether low-dose topical applications of difluoromethylornithine (DFMO) with or without Triamcinolone (Fougena, Melville, New York, U.S.A.) to moderately sun-damaged skin with actinic skin keratoses are efficacious.


METHODS
There were 4 topically administered, 6-month treatments, DFMO + Eucerin (Beiersdorf Inc., Hamburg, Germany), DFMO + Triamcinolone, Triamcinolone + Eucerin and Eucerin + Eucerin (to serve as double placebo). Participant eligibility included evidence of at least 2 actinic keratoses on each posterolateral forearm as well as moderate to severe evidence of sun-damaged skin, as evaluated by a board certified dermatologist. High resolution digitized imagery of nuclei from histologic sections of 4-mm punch biopsies from sun-damaged skin on the posterolateral forearms was recorded, at baseline and at the end of 6 months of study.


RESULTS
With 102 participants and 185 skin biopsies, a total of 16,395 skin cell nuclei were recorded. The nuclei were analyzed to assess the changes in the pattern of the nuclear chromatin. Two specific measures of end point evaluation were computed, including the percentage of nuclei with high values of nuclear abnormality and the reduction of the percentage of nuclei assigned by a discriminant function to the baseline data set. All 3 active interventions, including low-dose topical DFMO, topical Triamcinolone and topical DFMO + Triamcinolone, led to statistically significant reductions of both the number of nuclei with high nuclear abnormality as well as the number of nuclei assigned to the baseline data set. These reductions were found for all 3 treatments involving DFMO or Triamcinolone. For the placebo data sets only small, statistically insignificant increases or decreases of these percentages were observed.


CONCLUSIONS
The low-dose, topical drug interventions were all effective in reducing skin biopsy nuclear abnormality by a statistically significant 15-20%, whereas there was no evidence of a double placebo effect by karyometric assessment. These effects were greater than the case-to-case sampling error.
Bartels
Peter
P
College of Optical Sciences, University of Arizona, Tucson, Arizona 85724-5024, USA. hubertbartels@msn.com
Yozwiak
Michael
M
Einspahr
Janine
J
Saboda
Kathylynn
K
Liu
Yun
Y
Brooks
Christine
C
Bartels
Hubert
H
Alberts
David S
DS
D000287:Administration, Topical; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000627:therapeutic use*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D055623:Keratosis, Actinic / Q000473:pathology / Q000517:prevention & control*; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009823:Ointment Bases / Q000008:administration & dosage; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013472:Sunlight / Q000009:adverse effects; D014221:Triamcinolone / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D008055:Lipids; D009823:Ointment Bases; D014221:Triamcinolone; C039909:eucerin; D000518:Eflornithine