Pooled analysis of diarrhea events in patients with cancer treated with lapatinib.
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.
Crown
John P
JP
St Vincent's University Hospital, Dublin, Ireland, john.crown@icorg.ie
Burris
Harold A
HA
Boyle
Fran
F
Jones
Suzanne
S
Koehler
Maria
M
Newstat
Beth O
BO
Parikh
Roma
R
Oliva
Cristina
C
Preston
Alaknanda
A
Byrne
Julie
J
Chan
Steve
S
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
D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D005472:Fluorouracil