Dosing With 5% Imiquimod Cream 3 Times per Week for the Treatment of Actinic Keratosis

Korman, Neil J.; Moy, Ron; Ling, Mark; Matheson, Robert; Smith, Stacy; McKane, Scott; Lee, James H.

doi:10.1001/archderm.141.4.467

Cited by 145 publications

(29 citation statements)

References 18 publications

(17 reference statements)

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“…It is one of the most commonly used efficacy endpoints in AK clinical trials, and, as such, is commonly required for regulatory purposes. Some investigators, however, have challenged the clinical relevance of this endpoint and its clinical meaningfulness to the “real-world” setting [6–8]. As AKs are often numerous and difficult to see, clinical trials are often designed to treat a limited area (5 × 5 cm for example).…”

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confidence: 99%

“…This measure is further undermined by the chronic nature of AK which leads to lesions’ inevitable recurrence and subsequent re-treatment. Complete patient clearance results are not necessarily reflective of the overall long-term outcomes associated with AK lesions and tend to underestimate treatment benefits [6, 8]. For example, a lesion clearance rate of 90% (e.g., a reduction from 40 to 4 lesions) can be considered as a failure based on the complete patient clearance criteria, regardless of its obvious clinical relevance and patient benefit.…”

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confidence: 99%

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Use of Lesion Response Rate in Actinic Keratosis Trials

Szeimies

Atanasov

Bissonnette

2016

Dermatol Ther (Heidelb)

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Complete patient clearance is often required by regulatory agencies for the approval of treatments for actinic keratosis (AK). However, an increasing number of clinicians have challenged the use of this measure in clinical practice and its interpretation. It has been argued that complete patient clearance often underestimates the clinical benefit of a drug and is influenced by a number of key confounding factors, such as number and distribution of lesions, at baseline. Lesions response rate is one alternative which has been suggested as more relevant due to its applicability to clinical practice and closer reflection of the clinical value of the drug. This paper provides an updated perspective on the topic and details the current thinking on the role of complete clearance and lesion response rate in the context of AK. Funding: Galderma.

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confidence: 99%

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confidence: 99%

Use of Lesion Response Rate in Actinic Keratosis Trials

Szeimies

Atanasov

Bissonnette

2016

Dermatol Ther (Heidelb)

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“…AK are premalignant lesions that may progress to squamous cell carcinoma. IM administered twice per week for 16 weeks is an effective and well-tolerated treatment for AK [44,45]. Subclinical AK lesions may become apparent in the treatment area during treatment with IM.…”

Section: Table 1 Skin Disorders Treated With Topical Imiquimod Officmentioning

confidence: 99%

Topical Imiquimod: Mechanism of Action and Clinical Applications

Vidal¹

2006

MRMC

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“…However, several controlled clinical trials, as well as numerous case reports and smaller series of cases have demonstrated compellingly that imiquimod is also effective against a variety of primary skin cancers and cutaneous metastases of some malignancies. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas [6][7][8][9][10], keratoacanthomas [11,12], actinic keratoses [13][14][15][16][17] and Bowen´s disease [18,19], cutaneous metastases of melanoma [20][21][22][23][24], some cases of primary melanoma in situ [25][26][27][28][29] and cutaneous T cell lymphomas [30][31][32][33]. Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy [34][35][36] or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies [37,38].…”

Section: Introductionmentioning

confidence: 99%

The Antitumoral Mode of Action of Imiquimod and Other Imidazoquinolines

Schön

2007

CMC

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Imiquimod, the lead compound of the imidazoquinoline family of nucleoside analogues, has shown good efficacy against a variety of tumors of different origin. The mode of action of imiquimod and related compounds, which we have begun to understand in some detail in recent years, is complex and interesting inasmuch as it appears to comprise several presumably mutually enhancing components. Predominant amongst its actions is the induction of pro-inflammatory cytokines through agonistic activity towards Toll-like receptor (TLR)-7 and TLR-8, and consecutively, activation of the central transcription factor NF-kappaB. This activity stimulates the production of pro-inflammatory cytokines, chemokines and other mediators resulting in activation of antigen-presenting cells and the mounting of a profound Th1-weighted antitumoral cellular immune response. In addition, there are a number of secondary effects on the molecular and cellular level that can be explained through the activation of NF-kappaB. The pro-inflammatory activity of imiquimod appears to be augmented by suppression of a negative regulatory feedback mechanism which normally limits inflammatory responses. This is achieved independent of TLR-7 and TLR-8 through interference with adenosine receptor signaling pathways, particularly the A(2A) subtype, and receptor-independent reduction of adenylyl cyclase activity. Finally, at higher, albeit therapeutically relevant concentrations, imiquimod exerts a pro-apoptotic activity against tumor cells. Induction of apoptosis by imiquimod appears to be dependent on Bcl-2 proteins and involves caspase activation. The combination of multiple, presumably synergistic anti-tumoral functions by a single compound represents an interesting principle of pathogenesis-oriented, anti-neoplastic therapy.

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Dosing With 5% Imiquimod Cream 3 Times per Week for the Treatment of Actinic Keratosis

Cited by 145 publications

References 18 publications

Use of Lesion Response Rate in Actinic Keratosis Trials

Use of Lesion Response Rate in Actinic Keratosis Trials

Topical Imiquimod: Mechanism of Action and Clinical Applications

The Antitumoral Mode of Action of Imiquimod and Other Imidazoquinolines

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