Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm
| Autor: | Clara Curiel-Lewandrowski, Chengcheng Hu, Peter H. Bartels, Paul B. Myrdal, Janine G. Einspahr, Yira Bermudez, David S. Alberts, Michael Yozwiak, Joanne M. Jeter, James Warneke, Hubert G. Bartels, Steven P. Stratton |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research medicine.medical_specialty Diclofenac Eflornithine Skin Neoplasms Combination therapy Administration Topical Inflammation Gastroenterology law.invention 03 medical and health sciences 0302 clinical medicine Forearm Randomized controlled trial law Internal medicine medicine Anticarcinogenic Agents Humans Adverse effect Skin business.industry Anti-Inflammatory Agents Non-Steroidal Middle Aged Prognosis Surgery Discontinuation Keratosis Actinic stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Sunlight Female medicine.symptom business Follow-Up Studies medicine.drug |
| Zdroj: | Cancer Prevention Research. 9:128-134 |
| ISSN: | 1940-6215 1940-6207 |
| DOI: | 10.1158/1940-6207.capr-15-0232 |
| Popis: | 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. Cancer Prev Res; 9(2); 128–34. ©2015 AACR. See related article by Tsai and Hawk, p. 125 |
| Databáze: | OpenAIRE |
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