Topical 1% 5-fluoruracil as sole therapy safe, effective for OSSN
Use of topical 1% 5-fluoruracil (5-FU) as a sole therapy has shown its long-term safety and efficacy in patients with preinvasive ocular surface squamous neoplasia (OSSN) and for a limited proportion of invasive OSSN, according to a study.
Researchers included 41 patients affected by OSSN, each of whom underwent full ophthalmological examination at baseline, with cytological or histological confirmation. Patients received topical chemotherapy with 1% 5-FU four times a day for 4 weeks (one course). Adjunctive courses were administered after 1 month of chemotherapy-free interval. Mean follow-up was 105 months.
“Our treatment strategy is characterized by one (30 days) or more courses followed by 30 days of no treatment between each course,” researchers said. “The standard dosage of topical 5-FU reported is 1% in aqueous solution, used four times a day over 4 weeks.” [Int Ophthalmol Clin 2015;55:9–21]
Thirty-four (83 percent) cases achieved complete tumour regression after a mean of 1.5 courses (range, one to three courses). Complete response was significantly associated with tumour thickness <1.5 mm (p=0.005), lack of fornix or tarsal involvement (p=0.015 and p0.009, respectively), and the absence of multifocality (p=0.002) based on univariate analysis. [Br J Ophthalmol 2017;101:1094-1099]
“We achieved a complete clinical and cytological regression in 83 percent of treated lesions, after a mean of 1.5 1% 5-FU courses, with the longest follow-up ever reported,” researchers claimed.
In addition, incomplete tumour response was associated with histopathological diagnosis (intraepithelial neoplasia vs squamous cell carcinoma; p=0.019) and American Joint Committee on Cancer (AJCC) classification (T1 vs T2 or T3; p=0.028). Multivariate analysis revealed that only tumour thickness >1.5 mm (p=0.045) and multifocality (p=0.023) correlated with incomplete tumour response.
Nineteen (48 percent) eyes experienced transient and reversible low-to-mild local side effects.
“In our population, only transient and reversible low-to-mild 5-FU local side effects were documented in 48 percent of treated patients, including superficial punctate keratitis and conjunctival hyperaemia, according to previous published data. Moreover, treatment was never discontinued due to these side effects,” researchers said.
Compared with standard surgical excision, topical chemotherapy has several advantages, including the treatment of the entire ocular surface, targeting of the tumour cells, simplicity of treatment, reduced cost associated with avoidance of the surgical approach and reduced patient morbidity. [Ophthalmology 2000;107:2190–5]
“A relevant concern in the use of topical chemotherapy is that some patients may not be fully compliant with drug administration timing and dosage,” researchers said. “Nevertheless, in our experience, no cases of clinically significant lack of compliance were documented.”
“The main clinical limitation of this treatment is elevated tumour thickness (>1.5 mm) and tumour multifocality. Nevertheless, further prospective studies are essential before recommending 5-FU as a sole treatment of invasive OSSN,” they added.
Preinvasive and invasive OSSN represent the most common primary tumours of the eye, and their spectrum is represented by conjunctival and corneal dysplasia and squamous cell carcinoma. The standard treatment modality for OSSN, with recurrence rates ranging from 5 to 69 percent, is surgical excision. [Surv Ophthalmol 1995;39:429–50; Ophthalmology 2012;119:1974–81]
A shift from surgery alone to the use of topical chemotherapeutic agents alone or as adjuncts, before or after surgery, has been seen in the last 20 years, according to researchers. [Int Ophthalmol Clin 2015;55:9–21]