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New agents in the pipeline for the treatment of non-melanoma skin cancer

Stockfleth, E.

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doi: 10.1097/01.cmr.0000382774.21311.45
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In contrast to malignant melanoma or basal cell carcinoma, representing single tumors, actinic keratosis (AK) occur multiple in affected sun-exposed sites representing actinic field cancerisation. UV radiation induces something like a local immunosuppression: The immune cells of the skin (Langerhans cells) get downregulated; several mutations occur and oncogenes are expressed in the entire affected area. All stages – from subclinical AK to invasive squamous cell carcinoma – coexist at the same time. This phenomenon is referred to as ‘field cancerisation’.

‘Field cancerisation’ has important implications for the treatment of AK. The management of AK should therefore include the treatment of the whole actinically damaged area rather than the unspecific destruction of single lesions within the field. This ‘field-treatment’ approach leads to a more sustained clearance as both clinically visible and subclinical (‘sleeping’) AKs are treated at one timepoint and recurrence of AK from these subclinical lesions is reduced.

It is easy to understand that following the removal of a single lesion, for example by cryotherapy, a new tumor can rapidly develop only a few centimetres away, out of atypical keratinocytes carrying relevant mutations.

A range of treatment options are available for the management of AK, including methods to physically remove or destroy individual AK lesions (cryotherapy, curettage, dermabrasion, chemical peeling, photodynamic therapy and laser treatment) and topical treatments which aim to both remove the AK and to eliminate altered cells before they progress into invasive malignancies. Topical treatment options include 5-fluorouracil (5-FU) (a chemotherapeutic antimetabolite) imiquimod (an immune-response modifier and toll-like receptor 7 agonist) and diclofenac in hyaluronic acid (a non-steroidal anti-infl ammatory drug (NSAID) formulated in hyaluronic acid to ensure targeted delivery to the epidermis).

But there also are a lot of new upcoming, mainly topical treatment options like: a new concentration of imiquimod, a lower concentration of 5-fluorouracil 0.5%/salicylic acid 10.0%, or the topical use of PEP 005 which has the possible advantage, that the patients have to apply this substance only for 2 or 3 days.

For the selection of the appropriate treatment option several aspects have to be considered including duration, course and extent of the alterations, the location of the lesions and patient-specific characteristics like age, compliance, multi-morbidity and possibly immunosuppression. At the end of the day, the dermatologist, together with his patient has to make the final decision, which treatment option is the best for the patient. Maybe, the combination of a field directed treatment option with a lesion directed treatment option is the best for the daily practice.

© 2010 Lippincott Williams & Wilkins, Inc.