Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.
Abstract
Few epidemiologic studies describe longitudinal liver chemistry (LC) elevations in
cancer patients. A population-based retrospective cohort was identified from 31 Phase
2-3 oncology trials (excluding targeted therapies) conducted from 1985 to 2005 to
evaluate background rates of LC elevations in patients (n = 3998) with or without
liver metastases. Patients with baseline liver metastases (29% of patients) presented
with a 3% prevalence of alanine transaminase (ALT) ≥ 3x upper limits normal (ULN)
and 0.2% prevalence of bilirubin ≥ 3xULN. During follow-up, the incidence (per 1000
person-months) of new onset ALT elevations ≥3xULN was 6.1 (95% CI: 4.5, 8.0) and 2.2
(95% CI: 0.9, 4.5) in patients without and with liver metastases, respectively. No
new incident cases of ALT and bilirubin elevations suggestive of severe liver injury
occurred among those with liver metastases; a single case occurred among those without
metastasis. Regardless of the presence of liver metastases, LC elevations were rare
in cancer patients during oncology trials, which may be due to enrollment criteria.
Our study validates uniform thresholds for detection of LC elevations in oncology
studies and serves as an empirical referent point for comparing liver enzyme abnormalities
in oncology trials of novel targeted therapies. These data support uniform LC stopping
criteria in oncology trials.
Type
Journal articleSubject
Alanine aminotransferaseBilirubin
Clinical trial
Hepatotoxicity
Liver enzyme
Liver injury
Metastasis
Oncology
Truncated robust multivariate outlier detection
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https://hdl.handle.net/10161/11949Published Version (Please cite this version)
10.1016/j.yrtph.2016.03.019Publication Info
Shantakumar, Sumitra; Landis, Sarah; Lawton, Andy; & Hunt, Christine M (2016). Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical
trial cohort. Regul Toxicol Pharmacol, 77. pp. 257-262. 10.1016/j.yrtph.2016.03.019. Retrieved from https://hdl.handle.net/10161/11949.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Christine Marie Hunt
Adjunct Professor in the Department of Medicine

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