title: Lack of evidence for a link between latanoprost use and malignant melanoma: an analysis of safety databases and a review of the literature.
abstract: OBJECTIVE
  To determine if there is an association between the use of latanoprost ophthalmic solution and malignant melanoma and to assess the evidence of a plausible biological mechanism.
  
  
  METHODS
  Two safety databases were reviewed: one representing all latanoprost (n=24) and fixed-combination latanoprost/timolol (n=16) clinical trials conducted from November 1992 through November 2007 and a global safety database of all spontaneous non-trial-related clinical reports spanning 13 and 9 years for latanoprost and for latanoprost/timolol, respectively. A systematic PubMed search for studies evaluating potential mechanisms was conducted.
  
  
  RESULTS
  Amongst 12,880 latanoprost-treated subjects in clinical trials, no reported cases of ocular melanoma and three cases of cutaneous melanoma were identified. Of 19,940 cases recorded in the global safety database, 22 reports of ocular/cutaneous neoplasms were identified. Of these neoplasms, 11 were ocular and six were cutaneous melanomas. Possible association with latanoprost use could not be excluded in three ocular and one periorbital report. In vitro and in vivo data were consistent with a mechanism whereby the increased iris pigmentation results from stimulation of melanin synthesis by induction of tyrosinase transcription without increasing mitotic activity.
  
  
  CONCLUSIONS
  There is no evidence at present that establishes a link between latanoprost use and either ocular or cutaneous melanoma.
authors.affiliation: Pfizer Inc., 235 East 42nd Street, New York, NY 10017, USA. charles.s.tressler@pfizer.com
authors.forename: Charles S
authors.initials: CS
authors.lastname: Tressler
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wiseman
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Dombi
authors.forename: Bart
authors.initials: B
authors.lastname: Jessen
authors.forename: Kui
authors.initials: K
authors.lastname: Huang
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Kwok
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Wirostko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D004338:Drug Combinations; D019317:Evidence-Based Medicine / Q000379:methods; D005134:Eye Neoplasms / Q000139:chemically induced*; D005260:Female; D006801:Humans; D000077338:Latanoprost; D008297:Male; D008545:Melanoma / Q000139:chemically induced*; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000139:chemically induced; D013999:Timolol / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol