TY - JOUR
T1 - Randomized Trial of Four Treatment Approaches for Actinic Keratosis
AU - Jansen, Maud H. E.
AU - Kessels, Janneke P. H. M.
AU - Nelemans, Patty J.
AU - Kouloubis, Nina
AU - Arits, Aimee H. M. M.
AU - van Pelt, Han P. A.
AU - Quaedvlieg, Patricia J. F.
AU - Essers, Brigitte A. B.
AU - Steijlen, Peter M.
AU - Kelleners-Smeets, Nicole W. J.
AU - Mosterd, Klara
N1 - Funding Information:
Supported by a grant (80-83600-98-3054) from the Netherlands Organization for Health Research and Development (ZonMw), a governmental institution that finances research to improve health care in the Netherlands.
Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2019/3/7
Y1 - 2019/3/7
N2 - BACKGROUNDActinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.METHODSWe investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm(2), were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed.RESULTSA total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (PCONCLUSIONSAt 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments.
AB - BACKGROUNDActinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.METHODSWe investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm(2), were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed.RESULTSA total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (PCONCLUSIONSAt 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments.
KW - SQUAMOUS-CELL CARCINOMA
KW - MALIGNANT-TRANSFORMATION
KW - TREATMENT ALGORITHM
KW - SOLAR KERATOSES
KW - DOUBLE-BLIND
KW - REAL-WORLD
KW - CREAM
KW - GUIDELINES
KW - 5-PERCENT
KW - CHEMOPREVENTION
U2 - 10.1056/NEJMoa1811850
DO - 10.1056/NEJMoa1811850
M3 - Article
C2 - 30855743
SN - 0028-4793
VL - 380
SP - 935
EP - 946
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 10
ER -