Prevalence and incidence of liver enzyme elevations in a pooled oncology clinical trial cohort.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shantakumar, S; Landis, S; Lawton, A; Hunt, CM

Published Date

  • June 2016

Published In

Volume / Issue

  • 77 /

Start / End Page

  • 257 - 262

PubMed ID

  • 27025923

Pubmed Central ID

  • 27025923

Electronic International Standard Serial Number (EISSN)

  • 1096-0295

Digital Object Identifier (DOI)

  • 10.1016/j.yrtph.2016.03.019


  • eng

Conference Location

  • Netherlands