Phase IIB randomized study of topical difluoromethylornithine and topical diclofenac on sun-damaged skin of the forearm

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalCancer Prevention Research
Volume9
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Eflornithine
Diclofenac
Solar System
Forearm
Skin
Inflammation
Health Priorities
Skin Neoplasms
Squamous Cell Carcinoma
Biomarkers
Biopsy
Costs and Cost Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{e8799212eb6e4c3f8007b71cc51f6d96,
title = "Phase IIB randomized study of topical difluoromethylornithine and topical diclofenac on sun-damaged skin of the forearm",
abstract = "Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.",
author = "Jeter, {Joanne M} and Curiel, {Clara N} and Stratton, {Steven P} and Myrdal, {Paul B} and Warneke, {James A} and Einspahr, {Janine G} and Bartels, {Hubert G.} and Michael Yozwiak and Yira Bermudez and Chengcheng Hu and Peter Bartels and Alberts, {David S}",
year = "2016",
month = "2",
day = "1",
doi = "10.1158/1940-6207.CAPR-15-0232",
language = "English (US)",
volume = "9",
pages = "128--134",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - Phase IIB randomized study of topical difluoromethylornithine and topical diclofenac on sun-damaged skin of the forearm

AU - Jeter, Joanne M

AU - Curiel, Clara N

AU - Stratton, Steven P

AU - Myrdal, Paul B

AU - Warneke, James A

AU - Einspahr, Janine G

AU - Bartels, Hubert G.

AU - Yozwiak, Michael

AU - Bermudez, Yira

AU - Hu, Chengcheng

AU - Bartels, Peter

AU - Alberts, David S

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

AB - Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

UR - http://www.scopus.com/inward/record.url?scp=84957958604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84957958604&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-15-0232

DO - 10.1158/1940-6207.CAPR-15-0232

M3 - Article

C2 - 26712942

AN - SCOPUS:84957958604

VL - 9

SP - 128

EP - 134

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 2

ER -