Cutaneous Oncology: Clinical Pearls


George Martin, MD & Ted Rosen, MD

Why field therapy?

Data from Europe using a variety of techniques (including full face cross-polarized light examination, fluorescence photography, high definition optical coherence topography and reflectance confocal microscopy) clearly validate the concept of a “field” of abnormality in close spatial proximity to visible AK lesions.

Facial AKs:

Although we did not mention this in our talk, for those of you who use 5-FU, please remember that the Phase III data on 0.5% 5-FU demonstrated that 1 week of daily use of 0.5% 5-FU cleared nearly 75% of individual AKs. Try: 0.5% 5-FU QD x 1 week, wait 1 month, then follow with 2 -3 weeks QD application to “clean up” remaining AKs. This regiment has gained widespread acceptance by patients and physicians as a more tolerable field therapy. 5% 5-FU BID is equivalent to 0.5% 5-FU and can be used interchangeably.

Ingenol mebutate 0.015% applied nightly x 3 has been a remarkably effective therapy with great patient compliance. However, it’s FDA approval was for limited areas (25 cm2). As a full-face therapy, it appears very effective; however, controlled studies on “full face” clearance/efficacy is pending. Patients need to be counseled that they will experience a moderate to severe “sunburn-like” effect beginning 4 hours after application. This is likely due to its MOA, which includes a direct cytotoxic effect. Analgesia is generally required. Clinically, we have observed while treating full-face, ingenol mebutate is selective for AKs with mild/moderate erythema between AK lesions.

New data, both short term (11 weeks) and long term (one year), support the benefit of using ingenol mebutate in combination with standard liquid nitrogen cryotherapy. Cryotherapy is performed first, and then ingenol mebutate used per approved protocol three weeks late. At one year, the combination therapy has a higher complete clearance rate than cryotherapy followed by vehicle control. Off label, ingenol mebutate appears promising for the management of actinic cheilitis in the three day, FDA-approved regimen. More studies are needed to validate this idea.

If you perform PDT in your practice, and use 1 -> 3-hour ALA incubation periods, recent Phase II studies from DUSA show that 1, 2 or 3 hour incubation periods are roughly equally efficacious (35% – 50% clearance) but 2 treatments 8 weeks apart are required for most patients to achieve >70% individual lesion clearance. To maximize the efficacy of a 1-hour incubation, consider pre-treating with 5-FU for 1 week to the face or 10 days to the scalp then perform a 1 hr. ALA incubation. This combination will eliminate the need for a 2nd PDT. For those patients with refractory facial AKs, consider pretreating for 7 days with 3.75% imiquimod followed by ALA PDT (1-3 hour incubation). Excellent long-term results (18 months) have been observed when destructive techniques such as PDT are combined with immune modulators.

Can ALA PDT be “painless”?? Try incubating for 15 mins with ALA and then place the patient under the blue light for 1 hour. Preliminary results (G.Martin MD) demonstrate that ALA PDT as monotherapy or in combination with 5-FU or 3.75% imiquimod, employing this technique is in fact “painless”. Individual AK clearance rates of 50% were demonstrated in a proof of concept small patient study. Large-scale studies are warranted to determine efficacy. Network meta-analysis (comparing different techniques against one-another) suggest that PDT is the optimal field therapy for AKs.

The focus of PDT has been aimed at treating AKs. Is there evidence that PDT may prevent BCCs? Data from studies on basal-cell nevus syndrome patients demonstrate long-term clearance and prevention of new BCC development compared to non-treated areas of the trunk following ALA PDT using red light.

The use of 3.75% imiquimod for diffuse facial AKs while effective, results in substantial “downtime” of nearly 6 weeks. Consider 3.75% imiquimod QD x 7 days, 2 weeks rest, followed by once weekly applications. There will be some initial unsightliness during the 1 week of continuous use. Individual AKs are seen to clear with continuous application with minimal irritation. Chronic immune stimulation (>1 year) appears to be helpful in limiting AK recurrences and may prove over time to inhibit the development of invasive SCC. Large-scale studies are warranted.