title: Effect of topical imiquimod as primary treatment for lentigo maligna: the LIMIT-1 study.
abstract: BACKGROUND
  Topical imiquimod is sometimes used for lentigo maligna (LM) in situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression (pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod vs. surgery might be justified by a high imiquimod pCR rate.
  
  
  OBJECTIVE
  Primary: to estimate the pCR rate for LM following imiquimod. Secondary: to assess the accuracy of prediction of pCR, using clinical complete regression (cCR) plus negative post-treatment biopsies, tolerability, resource use, patients' preferences and induced melanoma immunity.
  
  
  METHODS
  This was a single-arm phase II trial of 60 imiquimod applications over 12 weeks for LM then radical resection. A pCR rate ≥ 25 out of 33 would reliably discriminate between pCR rates < 60% and ≥ 85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool.
  
  
  RESULTS
  The pCR rate was 10 of 27 (37%, 95% confidence interval 19-58%). The rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on subsequent surgery. The median dose intensity was 86·7%. Of the 16 surveyed patients, eight preferred primary imiquimod over surgery if the cure rate for imiquimod was 80%, and four of 16 if it was ≤ 40%.
  
  
  CONCLUSIONS
  The pCR rate was insufficient to justify phase III investigation of imiquimod vs.
  
  
  METHODS
  Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy.
authors.affiliation: University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, U.K.
authors.forename: J R
authors.initials: JR
authors.lastname: Marsden
authors.affiliation: Cancer Research U.K. Clinical Trials Unit, School of Cancer Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
authors.forename: R
authors.initials: R
authors.lastname: Fox
authors.affiliation: Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, U.K.
authors.forename: N M
authors.initials: NM
authors.lastname: Boota
authors.affiliation: Royal Surrey County Hospital, Guildford, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Cook
authors.affiliation: Cancer Research U.K. Clinical Trials Unit, School of Cancer Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Wheatley
authors.affiliation: Cancer Research U.K. Clinical Trials Unit, School of Cancer Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
authors.forename: L J
authors.initials: LJ
authors.lastname: Billingham
authors.affiliation: Cancer Research U.K. Clinical Trials Unit, School of Cancer Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
authors.forename: N M
authors.initials: NM
authors.lastname: Steven
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D018327:Hutchinson's Melanotic Freckle / Q000188:drug therapy*; D000077271:Imiquimod; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D000077271:Imiquimod