title: The effect of topical diclofenac 3% and calcitriol 3 μg/g on superficial basal cell carcinoma (sBCC) and nodular basal cell carcinoma (nBCC): A phase II, randomized controlled trial.
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.
  
  
  CONCLUSIONS
  The sample size was small.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Tjinta
authors.initials: T
authors.lastname: Brinkhuizen
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Kiki J A
authors.initials: KJ
authors.lastname: Frencken
authors.affiliation: Department of Epidemiology, CAPHRI (Care and Public Health Research Institute) School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Nelemans
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marlou L S
authors.initials: ML
authors.lastname: Hoff
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Nicole W J
authors.initials: NW
authors.lastname: Kelleners-Smeets
authors.affiliation: Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
authors.affiliation: Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Michiel P J
authors.initials: MP
authors.lastname: van der Horst
authors.affiliation: Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Dorit
authors.initials: D
authors.lastname: Rennspiess
authors.affiliation: Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Véronique J L
authors.initials: VJ
authors.lastname: Winnepenninckx
authors.affiliation: 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.
authors.forename: Maurice A M
authors.initials: MA
authors.lastname: van Steensel
authors.affiliation: Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands; GROW Research Institute for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Klara
authors.initials: K
authors.lastname: Mosterd
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005782:Gels; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009824:Ointments; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016037:Single-Blind Method; D012878:Skin Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D019394:Ki-67 Antigen; D009824:Ointments; D019253:Proto-Oncogene Proteins c-bcl-2; D014815:Vitamins; D004008:Diclofenac; D002117:Calcitriol
keywords: basal cell carcinoma; calcitriol; diclofenac; noninvasive; nonsteroidal anti-inflammatory drugs; targeted therapy; topical; vitamin D