Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8442132 | European Journal of Cancer | 2015 | 10 Pages |
Abstract
Drug-induced liver chemistry abnormalities, primarily transaminase elevations, are commonly observed in pazopanib-treated patients. This meta-analysis characterises liver chemistry abnormalities associated with pazopanib. Data of pazopanib-treated patients from nine prospective trials were integrated (NÂ =Â 2080). Laboratory datasets were used to characterise the incidence, timing, recovery and patterns of liver events, and subsequent rechallenge with pazopanib. Severe cases of liver chemistry abnormalities were clinically reviewed. Multivariate analyses identified predisposing factors. Twenty percent of patients developed elevated alanine aminotransferase (ALT) >3ÃULN. Incidence of peak ALT >3-5ÃULN, >5-8ÃULN, >8-20ÃULN and >20ÃULN was 8%, 5%, 5% and 1%, respectively. Median time to onset for all events was 42Â days; 91% of events were observed within 18Â weeks. Recovery rates based on peak ALT >3-5ÃULN, >5-8ÃULN, >8-20ÃULN and >20ÃULN were 91%, 90%, 90% and 64%, respectively. Median time from onset to recovery was 30Â days, but longer in patients without dose interruption. Based on clinical review, no deaths were associated with drug-induced liver injury. Overall, 38% of rechallenged patients had ALT elevation recurrence, with 9-day median time to recurrence. Multivariate analysis showed that older age was associated with development of ALT >8ÃULN. There was no correlation between hypertension and transaminitis. Our data support the current guidelines on regular liver chemistry tests after initiation of pazopanib, especially during the first 9 or 10Â weeks, and also demonstrate the safety of rechallenge with pazopanib.
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Authors
Thomas Powles, Sergio Bracarda, Mei Chen, Elliot Norry, Natalie Compton, Mark Heise, Thomas Hutson, Philipp Harter, Christopher Carpenter, Lini Pandite, Neil Kaplowitz,