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Ecase # D-8 Rick Ludwig, M.D. March 17-21, 2003 Actinic Keratosis Actinic Keratoses are commonly observed skin lesions, particularly in fair skinned, elderly patients with a history of excessive sun exposure (ie. most of them). Some of these lesions develop into squamous cell carcinomas. CC is a 92 yo man who presented with scaling of the upper portion of his left pinna. He was in remarkably good health, living independently with no significant chronic conditions. His lesion was initially treated as dermatitis with topical steroids and antibiotic ointment. It did not respond. He was referred to dermatology where the initial impression was a large basal cell carcinoma with multiple actinic keratoses on the face and forehead, and seborrhea of the face. However, on biopsy it was found to be a squamous cell carcinoma. He underwent Moh's surgery with removal of most of the left pinna. Several months later he presented with firm nodes in his left neck. These were biopsied and found to be SCC as well, presumably metastatic. He was irradiated and did well until last year when he began losing weight. A chest x-ray demonstrated metastatic lesions in both lungs. He remains at home with his wife and son under the care of hospice. Did Mr. C's cancer begin as an Actinic Keratosis? Probably, though not certainly. AK's are common on the ear, and 60% of SCC's of the skin are thought to begin as AK's. But, SCC's are found on skin that has never seen the sun as well. Could his cancer have been prevented by early treatment of an AK? Possibly, but not certainly. The aggressiveness of AK's is known to be variable, with some regressing spontaneously. This is an issue in how we decide on treatment. Will all AK's become SCC's? No, see above. It's thought that .25% to 1% of AK's will become SCC's if left alone. What should we do for these lesions? First, and most importantly, patients should be advised to use sunscreen every day all day regardless of their age and number of lesions. It has been shown that sun protection reduces the rate of growth of current lesions, and as we know decreases the appearance of new ones. An Australian article demonstrated a reduction in lesions with the use of sun protection. I recommend patients find a sunscreen they like and use it on their face every day regardless of their plans or the weather. It is not possible to treat ALL lesions on some patients, there simply are too many. But clearly those that are growing should be treated, as should larger ones. Cryotherapy is usually used, with a thaw time of 20 to 45 seconds. Care should be taken over nerves close to the surface (digital nerves). There is a risk of depigmentation, but most patients have fair skin and this is not an issue. In patients with many lesions, 5-fluorouracil (Efudex) can be used. The advantage is that it can treat many lesions at once and treats lesions that can't be seen or felt. There are three concentrations available, 1%, 2% and 5%. See abstract below for a study done with a new formulation of .5%, which I can't find on the market yet. Use of 1% or 2% twice daily on the face is appropriate for 2-4 weeks or until the erosive stage is reached. The follow -up application of hydrocortisone cream on the face to resolve inflammation is then used. For patient information see www.efudex.com References: Naylor, MF, Boyd, A, Smith, DW, et al. High sun protection factor sunscreens in the suppression of actinic neoplasia. Arch Dermatol 1995; 131:170. Marks, R, Foley, P, Goodman, G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 1986; 115:649. 6. Lubritz, RR, Smolewski, SA. Cryosurgery cure rate of actinic keratoses. J Am Acad Dermatol 1982; 7:631. 7. New treatments for actinic keratoses. Med Lett Drugs Ther 2002; 44:57. 8. Levy, S, Furst, K, Chern, W. A pharmacokinetic evaluation of 0.5% and 5% fluorouracil topical cream in patients with actinic keratosis. Clin Ther 2001; 23:908
BACKGROUND: Systemic absorption of topical fluorouracil, although usually low, may vary as a result of the specific skin disease, product formulation, and other factors. OBJECTIVE: The present study was conducted to determine the pharmacokinetic profile and tolerability of a new topical 0.5% fluorouracil cream formulation compared with that of a currently available topical formulation of 5% fluorouracil cream. METHODS: This was an open-label, parallel-group study in which patients with actinic keratosis (AK) were randomized to treatment with either topical 0.5% fluorouracil once daily or topical 5% fluorouracil twice daily for up to 28 days. RESULTS: Twenty-one patients (all white; mean age, 64 years) participated in the study, 11 receiving topical 0.5% fluorouracil and 10 receiving topical 5% fluorouracil. Ten patients receiving 0.5% fluorouracil and 7 patients receiving 5% fluorouracil completed the 28-day study. Plasma concentrations of fluorouracil were detectable in 3 of 10 patients treated with 0.5% fluorouracil and 9 of 10 patients treated with 5% fluorouracil; fluorouracil was detected in the urine of 5 and 9 patients, respectively. Despite the one-tenth difference in drug concentration between formulations, the cumulative amount excreted in the urine of the 0.5% fluorouracil group was approximately one fortieth that of the 5% fluorouracil group. This difference may be a result of variations in vehicle formulations. At least 1 adverse event was reported by 4 of 11 patients in the 0.5% fluorouracil group and all 10 patients in the 5% fluorouracil group. The most common adverse event, facial irritation, was evident with both formulations but reached a plateau during treatment with 0.5% fluorouracil. All patients treated with 0.5% fluorouracil tolerated the full course of therapy, whereas 3 patients in the 5% fluorouracil group discontinued treatment early. No serious treatment-related adverse events were reported. CONCLUSIONS: These data suggest that 0.5% fluorouracil has minimal systemic absorption and is well tolerated in patients with AK.
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