title: Pooled analysis of diarrhea events in patients with cancer treated with lapatinib.
abstract: OBJECTIVE
  To characterize diarrhea events in patients with cancer treated with lapatinib as monotherapy or in combination with capecitabine or taxanes.
  
  
  METHODS
  Eleven clinical trials (phase I, II, or III) in patients with metastatic cancer were analyzed. Lapatinib was administered at doses ranging from 1,000 to 1,500 mg/day as monotherapy (n = 926) or in combination with capecitabine (n = 198) or taxanes (n = 687). Diarrhea events were characterized based on severity, time to onset, duration, required interventions, and clinical outcomes.
  
  
  RESULTS
  In the pooled analysis of nine studies, diarrhea occurred in 55% of lapatinib-treated patients and 24% of patients not receiving lapatinib. All grade diarrhea occurred in 51% of patients treated with lapatinib monotherapy and 65% treated with lapatinib plus capecitabine. In a separate analysis, 48% of patients treated with lapatinib plus a taxane experienced diarrhea. Overall, most diarrhea events were grade 1/2. Grade 3 events occurred in <10% of patients and grade 4 events were rare (<or=1%). Most diarrhea events resolved with conventional approaches and without dose modification. Approximately 40% of patients treated with lapatinib monotherapy or combination therapy experienced a first diarrhea event within 6 days of treatment initiation, with a median duration of 7-9 days. Lapatinib-containing chemotherapy regimens do not cause severe diarrhea when proactive monitoring and intervention is introduced.
  
  
  CONCLUSIONS
  Most diarrhea events in lapatinib-treated patients are low grade, requiring infrequent lapatinib dose modification or interruption. Proactive management of diarrhea is crucial to prevent more serious complications in lapatinib-treated patients.
authors.affiliation: St Vincent's University Hospital, Dublin, Ireland, john.crown@icorg.ie
authors.forename: John P
authors.initials: JP
authors.lastname: Crown
authors.forename: Harold A
authors.initials: HA
authors.lastname: Burris
authors.forename: Fran
authors.initials: F
authors.lastname: Boyle
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jones
authors.forename: Maria
authors.initials: M
authors.lastname: Koehler
authors.forename: Beth O
authors.initials: BO
authors.lastname: Newstat
authors.forename: Roma
authors.initials: R
authors.lastname: Parikh
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliva
authors.forename: Alaknanda
authors.initials: A
authors.lastname: Preston
authors.forename: Julie
authors.initials: J
authors.lastname: Byrne
authors.forename: Steve
authors.initials: S
authors.lastname: Chan
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 / Q000009:adverse effects / Q000031:analogs & derivatives; D003967:Diarrhea / Q000209:etiology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077341:Lapatinib; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D005472:Fluorouracil