Imiquimod 3.75% Cream in Combination With Cryotherapy in the Treatment of Hypertrophic Actinic Keratoses
Status:
Unknown status
Trial end date:
2011-08-01
Target enrollment:
Participant gender:
Summary
Actinic keratoses (AK) are common cutaneous lesions associate with chronic ultraviolet
radiation exposure. While most authorities consider AK as a pre-malignant lesion, some
consider it as an incipient squamous cell carcinoma (SCC). In addition, the skin around
clinically obvious AK lesions has been subject to the same chronic ultraviolet exposure,
resulting in genetic damage and mutations, resulting in "field cancerization." Subclinical
AKs may progress to clinical AKs, or even de novo invasive SCCs.
Among the current therapies for the treatment of AK are excisional surgery, cryosurgery,
electrodessication and curettage, topical chemotherapy and light therapies. With cryotherapy,
treated lesion clearance rates at 3 months post-treatment after double-freeze thaw
cryotherapy has been reported to be around 76-88%; Overall lesion clearance rate at
approximately 5 months post-cryosurgery has been reported to be 35-51%.
Imiquimod is a topical immune response modifier and a 5% formulation has been approved for
the treatment of AKs in the US as a 2x/week for 16 week regimen and in Europe as a 3x/week
for 4 week regimen for 1 or 2 courses of therapy. Topical imiquimod treatment may also reduce
subclinical lesions in the treatment area, resulting in fewer "new" AK lesions developing
over the same period of time when compared to focal treatment. In a comparison of cryosurgery
versus imiquimod for the treatment of AKs, Krawtchenko et al reported initial complete
clearance rates of 68 and 85% by clinical assessment, respectively. However, the treatment
field sustained clearance rate was 4% versus 73%, respectively. Tan et al reported that while
application of imiquimod or vehicle following cryosurgery resulted in comparable target AK
clearance rates at 12 weeks of 79% versus 76%, respectively, the imiquimod group had fewer
total AKs and fewer subclinical AKs.
Imiquimod cream at a concentration of 3.75% has been found in Phase 3 studies to be superior
to placebo cream with respect to clearance of AKs using a regimen of up to 2 packets (250 mg
of cream per packet, 500 mg total) applied daily to the entire face (approximately 200 cm2)
for two 2-week treatment cycles separated by a 2-week no-treatment period. This study aims to
examine the benefit of cryotherapy in combination with imiquimod 3.75% compared to
cryotherapy alone.