title: Analysis of dermatologic events in patients with cancer treated with lapatinib.
abstract: OBJECTIVE
  Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized.
  
  
  METHODS
  Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n=928) or in combination with paclitaxel or capecitabine (n=491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions.
  
  
  RESULTS
  Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in <or=8% of patients. Most DEs developed between days 1 and 14 of starting treatment, with a median duration of 29 days. Three percent of DEs led to lapatinib dose reduction, 7% resulted in dose interruption, and 1% led to drug discontinuation.
  
  
  CONCLUSIONS
  Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.
authors.affiliation: Department of Dermatology, Northwestern University, 676 North St. Claire Street, Suite 1600, Chicago, IL 60611-2941, USA. m-lacouture@northwestern.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Lacouture
authors.forename: S M
authors.initials: SM
authors.lastname: Laabs
authors.forename: M
authors.initials: M
authors.lastname: Koehler
authors.forename: R W
authors.initials: RW
authors.lastname: Sweetman
authors.forename: A J
authors.initials: AJ
authors.lastname: Preston
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
authors.forename: H L
authors.initials: HL
authors.lastname: Gomez
authors.forename: V M
authors.initials: VM
authors.lastname: Salazar
authors.forename: J A
authors.initials: JA
authors.lastname: Byrne
authors.forename: K M
authors.initials: KM
authors.lastname: Koch
authors.forename: K L
authors.initials: KL
authors.lastname: Blackwell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D000069287:Capecitabine; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005076:Exanthema / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects*; D012871:Skin Diseases / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D066246:ErbB Receptors; D017239:Paclitaxel; D005472:Fluorouracil