title: Topical fluorouracil after surgery for ocular surface squamous neoplasia in Kenya: a randomised, double-blind, placebo-controlled trial.
abstract: Ocular surface squamous neoplasia (OSSN) is an aggressive eye tumour particularly affecting people with HIV in Africa. Primary treatment is surgical excision; however, tumour recurrence is common. We assessed the effect of fluorouracil 1% eye drops after surgery on recurrence.
  
  
  
  We did this multicentre, randomised, placebo-controlled trial in four centres in Kenya. We enrolled patients with histologically proven OSSN aged at least 18 years. After standard surgical excision, participants were randomly allocated to receive either topical fluorouracil 1% or placebo four times a day for 4 weeks. Randomisation was stratified by surgeon, and participants and trial personnel were masked to assignment. Patients were followed up at 1 month, 3 months, 6 months, and 12 months. The primary outcome was clinical recurrence (supported by histological assessment where available) by 1 year, and analysed by intention to treat. The sample size was recalculated because events were more common than anticipated, and trial enrolment was stopped early. The trial was registered with Pan-African Clinical Trials Registry (PACTR201207000396219).
  
  
  
  Between August, 2012, and July, 2014, we assigned 49 participants to fluorouracil and 49 to placebo. Four participants were lost to follow-up. Recurrences occurred in five (11%) of 47 patients in the fluorouracil group and 17 (36%) of 47 in the placebo group (odds ratio 0·21, 95% CI 0·07-0·63; p=0·01). Adjusting for passive smoking and antiretroviral therapy had little effect (odds ratio 0·23; 95% CI 0·07-0·75; p=0·02). Adverse effects occurred more commonly in the fluorouracil group, although they were transient and mild. Ocular discomfort occurred in 43 of 49 patients in the fluorouracil group versus 36 of 49 in the placebo group, epiphora occurred in 24 versus five, and eyelid skin inflammation occurred in seven versus none.
  
  
  
  Topical fluorouracil after surgery substantially reduced recurrence of OSSN, was well-tolerated, and its use recommended.
  
  
  
  British Council for Prevention of Blindness and the Wellcome Trust.
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK; Department of Ophthalmology, University of Nairobi, Nairobi, Kenya. Electronic address: stephen.gichuhi@lshtm.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gichuhi
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Ephantus
authors.initials: E
authors.lastname: Macharia
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Joy
authors.initials: J
authors.lastname: Kabiru
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Alain M'bongo
authors.initials: AM
authors.lastname: Zindamoyen
authors.affiliation: Kitale District Hospital, Kitale, Kenya.
authors.forename: Hilary
authors.initials: H
authors.lastname: Rono
authors.affiliation: Sabatia Eye Hospital, Wodanga, Kenya.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ollando
authors.affiliation: Kenyatta National Hospital, Nairobi, Kenya.
authors.forename: Joseph
authors.initials: J
authors.lastname: Wachira
authors.affiliation: Kenyatta National Hospital, Nairobi, Kenya.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Munene
authors.affiliation: UHEAL Foundation, Nairobi, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Maina
authors.affiliation: Department of Pathology, MP Shah Hospital, Nairobi, Kenya.
authors.forename: Timothy
authors.initials: T
authors.lastname: Onyuma
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, UK; Moorfields Eye Hospital, London, UK; St Bartholomew's Hospital, London, London, UK.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Sagoo
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK; Moorfields Eye Hospital, London, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burton
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000601:surgery; D004311:Double-Blind Method; D005123:Eye / Q000473:pathology*; D005134:Eye Neoplasms / Q000473:pathology / Q000601:surgery*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007630:Kenya; D007766:Lacrimal Apparatus Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil