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Cidofovir (HPMPC), an acyclic nucleoside phosphonate analogue, is a promising drug that acts against a wide number of DNA viruses.1 In 1997, the US Federal Food and Drug Administration approved cidofovir (for intravenous use only) for the treatment of cytomegalovirus retinitis in patients with AIDS.1 Over the last few years, cidofovir in a 1–3% gel or cream vehicle has been found to be effective against unmanageable viral cutaneous lesions induced by herpes, pox, and papilloma families.2 Recent studies have explored intralesional administration of cidofovir for the treatment of HPV related tumours, such as cervical epithelial neoplasia, oesophageal carcinomas, and HSV-8 induced Kaposi’s sarcoma.3–6 We report a squamous cell carcinoma (SCC) of the eyelid which was successfully treated with intralesional cidofovir.
A 70 year old man presented with a nodular lesion 10 × 14 mm in size on his right lower eyelid, which had appeared 3 months earlier (Fig 1). The patient, who was otherwise in good general condition, reported a history of chronic, intense solar radiation exposure because he had lived in Somalia for many years. In the past 3 years he had been repeatedly treated with liquid nitrogen for multiple actinic keratosis of his forehead and upper eyelids. The clinical diagnosis of cutaneous SCC was confirmed by the histological examination of a punch biopsy. As the patient refused conventional surgery, after obtaining written consent the lesion was treated with a dose of cidofovir 0.1 ml (7.5 mg of active principle). The drug was injected both intralesionally and perilesionally with a fine needle (26 gauge). Care was taken to avoid intravascular inoculation. Erythema and ulceration were evident after 3 days, then the lesion became progressively smaller and flatter until it disappeared within the month. A skin punch biopsy was performed after 12 months on the previous lesional area, but revealed no presence of neoplastic cells. No systemic side effects were noted and the cosmetic result was excellent (Fig 2). The patient is free from recurrences after a 24 month follow up.
Surgical excision is the treatment of choice for SCC.7 Alternatively, liquid nitrogen, electrocautery, radiotherapy, or laser photocoagulation may be used. Decisions regarding treatment depend on the age of the patient, the location, extension, and severity of the neoplasm. For cases in which surgery or alternative cytodestructive techniques are not practical, local treatment with 5-fluorouracil, nitrogen mustard, bleomycin, mitomycin C, photodynamic therapy, or imiquimod may be considered as an alternative therapeutic option.7 Recent studies have showed that cidofovir exerts tumoricidal activity towards HPV related cervical intraepithelial neoplasia,3 oesophageal and respiratory papillomatous tumours,4,5 or HSV-8 related Kaposi’s sarcoma.6 To our knowledge, the regression of SCC after the intralesional injection of cidofovir has not previously been reported.
The mechanism of cidofovir as an antineoplastic agent is unknown. The involution of the neoplastic tissue could be due to the inhibition of rapidly proliferating cells through a decrease in DNA thymidine incorporation, the activation of tumour suppressor genes, the induction of apoptosis, and the inhibition of angiogenesis.8–10
Systemic administration of cidofovir is burdened with serious, dose related side effects. Kidney toxicity is the most common but less frequently uveitis, macular oedema, neutropenia, thrombocytopenia, nausea, fever, hair loss, and muscle pain have also been observed.2 When administered topically or intralesionally cidofovir has not, to date, shown systemic toxicity.
Surgical excision remains the best possible treatment for SCC, as it is usually curative and permits the histopathological evaluation of margins. However, the successful outcome with intralesional cidofovir in this case might be worth considering.