TY - JOUR

T1 - Improving the efficacy of photodynamic therapy for actinic keratosis

T2 - A comprehensive review of pharmacological pretreatment strategies

AU - Pihl, Celina

AU - Lerche, Catharina M.

AU - Andersen, Flemming

AU - Bjerring, Peter

AU - Haedersdal, Merete

N1 - Publisher Copyright: © 2023

PY - 2023

Y1 - 2023

N2 - Background: Photodynamic therapy (PDT) is approved for treatment of actinic keratoses (AKs) and field-cancerisation. Pretreatment with pharmacological compounds holds potential to improve PDT efficacy, through direct interaction with PpIX formation or through an independent response, both of which may improve PDT treatment. Objective: To present the currently available clinical evidence of pharmacological pretreatments prior to PDT and to associate potential clinical benefits with the pharmacological mechanisms of action of the individual compounds. Methods: A comprehensive search on the Embase, MEDLINE, and Web of Science databases was performed. Results: In total, 16 studies investigated 6 pretreatment compounds: 5-fluorouracil (5-FU), diclofenac, retinoids, salicylic acid, urea, and vitamin D. Two of these, 5-FU and vitamin D, robustly increased the efficacy of PDT across multiple studies, illustrated by mean increases in clearance rates of 21.88% and 12.4%, respectively. Regarding their mechanisms, 5-FU and vitamin D both increased PpIX accumulation, while 5-FU also induced a separate anticarcinogenic response. Pretreatment with diclofenac for four weeks improved the clearance rate in one study (24.9%), administration of retinoids had a significant effect in one of two studies (16.25%), while salicylic acid and urea did not lead to improved PDT efficacy. Diclofenac and retinoids demonstrated independent cytotoxic responses, whereas salicylic acid and urea acted as penetration enhancers to increase PpIX formation. Conclusion: 5-FU and vitamin D are well-tested, promising candidates for pharmacological pretreatment prior to PDT. Both compounds affect the haem biosynthesis, providing a target for potential pretreatment candidates. Key Words: Photodynamic Therapy, Actinic Keratosis,Pre-tretment,Review,enhancement

AB - Background: Photodynamic therapy (PDT) is approved for treatment of actinic keratoses (AKs) and field-cancerisation. Pretreatment with pharmacological compounds holds potential to improve PDT efficacy, through direct interaction with PpIX formation or through an independent response, both of which may improve PDT treatment. Objective: To present the currently available clinical evidence of pharmacological pretreatments prior to PDT and to associate potential clinical benefits with the pharmacological mechanisms of action of the individual compounds. Methods: A comprehensive search on the Embase, MEDLINE, and Web of Science databases was performed. Results: In total, 16 studies investigated 6 pretreatment compounds: 5-fluorouracil (5-FU), diclofenac, retinoids, salicylic acid, urea, and vitamin D. Two of these, 5-FU and vitamin D, robustly increased the efficacy of PDT across multiple studies, illustrated by mean increases in clearance rates of 21.88% and 12.4%, respectively. Regarding their mechanisms, 5-FU and vitamin D both increased PpIX accumulation, while 5-FU also induced a separate anticarcinogenic response. Pretreatment with diclofenac for four weeks improved the clearance rate in one study (24.9%), administration of retinoids had a significant effect in one of two studies (16.25%), while salicylic acid and urea did not lead to improved PDT efficacy. Diclofenac and retinoids demonstrated independent cytotoxic responses, whereas salicylic acid and urea acted as penetration enhancers to increase PpIX formation. Conclusion: 5-FU and vitamin D are well-tested, promising candidates for pharmacological pretreatment prior to PDT. Both compounds affect the haem biosynthesis, providing a target for potential pretreatment candidates. Key Words: Photodynamic Therapy, Actinic Keratosis,Pre-tretment,Review,enhancement

KW - 5-fluorouracil

KW - Actinic keratosis

KW - Cytotoxicity

KW - Dermatology

KW - Diclofenac

KW - Penetration enhancers

KW - Photodynamic therapy

KW - Retinoids

KW - Salicylic acid

KW - Urea

KW - Vitamin D

U2 - 10.1016/j.pdpdt.2023.103703

DO - 10.1016/j.pdpdt.2023.103703

M3 - Review

C2 - 37429460

AN - SCOPUS:85166667244

VL - 43

JO - Photodiagnosis and Photodynamic Therapy

JF - Photodiagnosis and Photodynamic Therapy

SN - 1572-1000

M1 - 103703

ER -