title: Rash with the multitargeted kinase inhibitors nilotinib and dasatinib: meta-analysis and clinical characterization.
abstract: OBJECTIVE
  Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors approved for the treatment of chronic myeloid leukemia (CML). In clinical trials, they have both been reported to cause rash in a significant number of patients, but its incidence varies significantly and has not been characterized clinically or histologically. The aim of this study was to determine the incidence of rash with nilotinib and dasatinib, and to provide a clinical and histopathological description of the rash.
  
  
  METHODS
  We conducted a meta-analysis of clinical trials evaluating nilotinib and dasatinib to determine and compare the incidence of rash with these medications. Additionally, we performed a retrospective chart review to analyze the clinical presentation and histology of patients presenting with rash.
  
  
  RESULTS
  The incidence of all-grade (grade 1-4) rash with nilotinib was 34.3% (95% CI, 27.9-41.3), higher (P = 0.017) than with dasatinib (23.3%; 95% CI, 18.8-28.6). Similarly, the incidence of high-grade rash with nilotinib (2.6%; 95% CI, 2.1-3.4) was higher (P = 0.002) than with dasatinib (1.1%; 95% CI, 0.8-1.6). The clinical presentation often consisted of a pruritic, perifollicular hyperkeratotic, occasionally erythematous papular rash affecting most areas of the body, depending on the severity.
  
  
  CONCLUSIONS
  Both nilotinib and dasatinib are associated with rash in a significant number of patients. Further studies to prevent and treat rash with nilotinib and dasatinib are required to improve patient quality of life, adherence with therapy and oncologic outcome.
authors.affiliation: Division of Dermatology, Department of Medicine, University of Toronto.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Drucker
authors.forename: Shenhong
authors.initials: S
authors.lastname: Wu
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Ellin
authors.initials: E
authors.lastname: Berman
authors.forename: Iris
authors.initials: I
authors.lastname: Amitay-Laish
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000069439:Dasatinib; D003875:Drug Eruptions / Q000453:epidemiology / Q000517:prevention & control*; D005076:Exanthema / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D019983:Guideline Adherence; D006801:Humans; D015994:Incidence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000453:epidemiology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D011788:Quality of Life; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; C498826:nilotinib; D000069439:Dasatinib