title: Retarded low-dose doxycycline for EGFR or MEK inhibitor-induced papulopustular rash.
abstract: BACKGROUND
  Epidermal growth factor receptor inhibitors (EGFRi) and MEK inhibitors (MEKi) are notorious for causing papulopustular rash. Treatment recommendations from studies and expert panels include, amongst others, oral tetracyclines. The efficacy of retarded low-dose doxycycline (rld-doxycycline), however, has not been investigated. The objective was to review the response and development of EGFRi- and MEKi-induced rash under therapy with rld-doxycycline.
  
  
  METHODS
  A retrospective review of all patients treated with rld-doxycyline 40 mg once daily between September 2011 and June 2012 for papulopustular rash. Rash development and severity (according to the Common Terminology Criteria of Adverse Events V4.0) were assessed.
  
  
  RESULTS
  Seventeen patients (13 men, 4 women) were treated with rld-doxycycline while receiving EGFRi [monoclonal antibodies (mab) n = 8, tyrosine kinase inhibitors (TKi) n = 7] or MEKi (n = 2). In 47% (n = 8) the rash was reduced by at least one grade, in 29% (n = 5) the rash was stabilized, 24% (n = 4) did not profit from the treatment. All patients treated with an EGFR-TKi or a MEKi profited of the rld-doxycycline. All patients who experienced deterioration were on treatment with an EGFR-mab.
  
  
  CONCLUSIONS
  Rld-doxycyline can improve EGFR-TKi- and MEKi-induced rash severity. Its effectiveness appears to be inferior to doxycycline 200 mg/day in more severe cases and in EGFR-mab-induced rash, but due to the advantageous side-effect profile, rld-doxycycline should be considered as a possible treatment option for papulopustular rash. Prospective, randomized trials are necessary to confirm these findings.
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Vaubel
authors.forename: E
authors.initials: E
authors.lastname: Livingstone
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: L
authors.initials: L
authors.lastname: Zimmer
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005076:Exanthema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors; D020930:MAP Kinase Kinase Kinases; D004318:Doxycycline