Tjinta Brinkhuizen1, Kiki J A Frencken2, Patty J Nelemans3, Marlou L S Hoff4, Nicole W J Kelleners-Smeets2, Axel Zur Hausen5, Michiel P J van der Horst5, Dorit Rennspiess5, Véronique J L Winnepenninckx5, Maurice A M van Steensel6, Klara Mosterd2. 1. Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. Electronic address: t.brinkhuizen@mumc.nl. 2. Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 3. Department of Epidemiology, CAPHRI (Care and Public Health Research Institute) School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands. 4. Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands. 5. Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 6. Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands; Institute of Medical Biology, Immunos, Singapore; Cancer Research Division, School of Medicine, Dentistry, and Nursing, Division of Biological Chemistry and Drug Development, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
Abstract
BACKGROUND:Nonsteroidal anti-inflammatory drugs and vitamin-D derivatives can target signaling pathways activated in basal cell carcinoma (BCC). OBJECTIVE: We investigated the efficacy of topically applied diclofenac sodium 3% gel, calcitriol 3 μg/g ointment, and a combination of both in superficial BCC (sBCC) and nodular BCC. METHODS:Patients with a primary, histologically proven sBCC (n = 64) or nodular BCC (n = 64) were randomized to topical diclofenac, calcitriol, combination of both, or no topical treatment (control group). After self-application twice daily under occlusion (8 weeks), tumors were excised. Primary outcome was posttreatment expression levels of proliferation (Ki-67) and antiapoptosis (B-cell lymphoma [Bcl-2]) immunohistochemical markers. Secondary outcomes were histologic clearance, adverse events, application-site reactions, and patient compliance. RESULTS:sBCC treated with diclofenac showed a significant decrease in Ki-67 (P < .001) and Bcl-2 (P = .001), and after combination therapy for Ki-67 (P = .012). Complete histologic tumor regression was seen in 64.3% (P = .0003) of sBCC (diclofenac) and 43.8% (P = .007) of sBCC (combination therapy) compared with 0.0% of controls. No significant changes were found in nodular BCC. Application-site reactions were mostly mild to moderate. LIMITATIONS: The sample size was small. CONCLUSION: Our results suggest that topical diclofenac is a promising new treatment for sBCC. Its mode of action differs from available noninvasive therapies, and thus has an additive value.
RCT Entities:
BACKGROUND: Nonsteroidal anti-inflammatory drugs and vitamin-D derivatives can target signaling pathways activated in basal cell carcinoma (BCC). OBJECTIVE: We investigated the efficacy of topically applied diclofenac sodium 3% gel, calcitriol 3 μg/g ointment, and a combination of both in superficial BCC (sBCC) and nodular BCC. METHODS:Patients with a primary, histologically proven sBCC (n = 64) or nodular BCC (n = 64) were randomized to topical diclofenac, calcitriol, combination of both, or no topical treatment (control group). After self-application twice daily under occlusion (8 weeks), tumors were excised. Primary outcome was posttreatment expression levels of proliferation (Ki-67) and antiapoptosis (B-cell lymphoma [Bcl-2]) immunohistochemical markers. Secondary outcomes were histologic clearance, adverse events, application-site reactions, and patient compliance. RESULTS:sBCC treated with diclofenac showed a significant decrease in Ki-67 (P < .001) and Bcl-2 (P = .001), and after combination therapy for Ki-67 (P = .012). Complete histologic tumor regression was seen in 64.3% (P = .0003) of sBCC (diclofenac) and 43.8% (P = .007) of sBCC (combination therapy) compared with 0.0% of controls. No significant changes were found in nodular BCC. Application-site reactions were mostly mild to moderate. LIMITATIONS: The sample size was small. CONCLUSION: Our results suggest that topical diclofenac is a promising new treatment for sBCC. Its mode of action differs from available noninvasive therapies, and thus has an additive value.
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