OCULAR CANCERS

Topical treatments show promise for treating several nonmelanoma periocular lesions, Robert C Kersten MD, University of California-San Francisco, US, told the American Academy of Ophthalmology. For patients with lentigo maligna, or extensive superficial or in situ squamous cell carcinomas, the topical immune sensitizer imiquimod, with close follow-up, may help avoid the cost, morbidity and cosmetic disfigurement of surgical excision. For non-cancerous infantile hemangioma, early trials suggest topical timolol is an effective treatment without the systemic side effects of traditional steroid therapy, Dr Kersten said.

Avoid side-effects

Initially approved by the US FDA for treatment of genital warts in 1997, imiquimod was approved for actinic keratoses and superficial basal cell carcinomas in 2004, Dr Kersten noted. Overall, it has proven more effective as a topical treatment for non-melanoma skin lesions than 5-flourouracil. To avoid side effects such as burning itching, pain crusting and ulceration, imiquimod is applied as a five per cent cream five days a week with two days vacation for six to 12 weeks, Dr Kersten said. Imiquimod boosts immune response to lesions by binding to toll-like receptor 7, inducing transcription of interferon-a, interferon-g and tumor necrosis factor. A five-day-a-week regimen for six weeks results in about 80 per cent clearance of superficial squamous cell carcinomas. However, placebo control studies also show a six per cent to nine per cent clearance histologically 12 to 18 weeks after biopsy, of squamous cell carcinomas which were biopsied but received no further pharmacologic treatment, Dr Kersten noted.

“The immune system may work on its own better than we expect to clear small lesions.†Imiquimod was less effective with nodular basal cell lesions, resulting in late recurrence. This suggests that the topical compound may not penetrate far enough to completely reach the lesion, Dr Kersten said. For squamous cell in situ lesions, topical imiquimod achieved about an 80 per cent clearance rate in follow-up of six to 31 months, making it a suitable alternative to surgery, Dr Kersten said. For invasive squamous cell lesions, the 71 per cent clearance rate is not sufficient due to the highly invasive nature of this condition. Current recommendations for imiquimod are for actinic keratoses, squamous cell in situ and superficial basal cell carcinoma of the trunk and extremities. Small series case reports suggest that ocular side effects are mild, with 15 patients developing conjunctivitis and six per cent ocular stinging, but no permanent side effects in one 47-patient study, Dr Kersten said.

“The good news is the side effects of imiquimod appear to be very manageable.†Imiquimod also has achieved a 50 per cent clearance rate with lentigo maligna, Dr Kersten said. While this seems low, it is useful because it eliminates half of the population that must be followed for progression to malignant disease, he added. About six per cent to seven per cent of patients progress, with older patients having less risk, which makes monitoring an acceptable strategy rather than subjecting all patients to surgery.