Topical Therapies

Topical therapies for premalignant penile lesions can take the form of chemotherapy or immunotherapy. They are best suited to immunocompetent patients with well-defined solitary lesions although there is a poor response rate in the immuno-suppressed or those with widespread 'field changes'.61 Lesions amenable to treatment with topical therapy include PIN, BP, and PKMB. They are not suitable for LS, GCA, or cutaneous horn.

5.6.1.1 5-Fluorouracil

The most common first-line treatment is topical 5% 5-Fluorouracil (5-FU or 5-flu-oro-2,4(1H, 3H)-pyrimidinedione; chemical formula C4H3FN2O2). This antimetabo-lite chemotherapeutic agent is a pyrimidine analogue. It is metabolized both inside cells and by the liver and excreted by the kidneys. It non-competitively inhibits thy-midylate synthase, reducing the production of thymidine. When inside the cell it is transformed into several cytotoxic metabolites that become incorporated into RNA and DNA, triggering cell cycle arrest and apoptosis. Its actions are S phase specific.

Protocols vary among clinicians on how frequently the 5-FU is applied. When applied topically between 4 and 6 weeks on alternate days, it is safe, with low morbidity and minimal systemic absorption. Patients are advised to apply the topical cream with or without gloves provided that thorough hand washing is performed following application. The treated area often becomes encrusted and inflamed during the treatment period and patients should be advised to expect this and continue treatment (Figs. 5.9 and 5.10). Additional application of topical steroid can be used if the areas become uncomfortable during the treatment period. It can take between 4 and 8 weeks for the areas to heal. Early studies reported sustained response rates approaching 100% at 5 years, although the numbers of patients treated in these studies are small (<10).62

5.6.1.2 Imiquimod

Non or partial responders to topical 5-FU can be treated with immunotherapy using topical 5% Imiquimod cream for a similar length of time as second-line treatment.63 The exact mechanism of action of this novel immunomodulatory therapy is unclear. It is known to utilize the toll-like receptor 7 to activate immune cells, to secrete cytokines such as interferon-a, tumor necrosis factor and various interleukins (IFNa, IL-1,6,12, TNFa) . Langerhan's cells in the skin are also activated and

Fig. 5.9 CIS of the glans penis before starting treatment with topical 5-FU

Fig. 5.9 CIS of the glans penis before starting treatment with topical 5-FU

Fig. 5.10 Same area of CIS following topical treatment with 5-FU

Fig. 5.10 Same area of CIS following topical treatment with 5-FU

migrate to local lymph nodes and trigger the adaptive immune system. Other cells believed to be activated are natural killer cells, macrophages, and B lymphocytes. Imiquimod can be applied for 5 days a week for a period of 4-6 weeks. The frequency of application can be reduced provided that the inflammatory response is maintained.64,65 While success has been reported in a number of case reports,63 and small case series,61 no large-scale long-term efficacy data are currently available.

5.6.1.3 Other Topical Agents

Other topical therapies include the use of 2-3% testosterone propionate or 0.05% clobetasol propionate for LS. Small case series from the late 1970s and 1980s reported favorable outcomes with topical testosterone.66,67 A study comparing these two treatments for vulval LS reported 6 month response rates of 77.5% and 91.7%, respectively, with recurrence rates of 20% and 6.7% in the 2 groups.68 However, the use of these treatments has never become established for penile LS. Given the long latency to invasive SCC in patients with LS, any possible beneficial effect in preventing malignant transformation would be difficult to prove.

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment