Abstract #2142: Liver enzyme elevations among cancer patients:
Results from a pooled clinical trial cohort

Abstract

There is a paucity of epidemiologic studies investigating elevated liver function tests (LFT) among cancer patients, with the majority of data coming from case reports or clinical trial adverse event reports. Data describing LFT elevations in cancer patients would aid patient safety by providing an empirical-based context for setting study drug cessation thresholds, and informing trial exclusion criteria. We performed a retrospective pooled analysis of oncology clinical trials conducted by GlaxoSmithKline between 1985-2005 to assess the baseline prevalence and incidence of LFT elevations in cancer patients. Alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (BILI) were examined as upper limits of normal using gender-specific normal range. A combination of AST or ALT \#8805;3x ULN + BILI \#8805;2x ULN + ALP <2x ULN that identifies potentially significant liver disease was also investigated. For each selected cutpoint or combination, the baseline prevalence of elevations before administration of study treatment was calculated. The cumulative incidence and person-time incidence rates (IR) of new elevations occurring during follow-up were calculated among patients who had normal liver chemistries at baseline. 95% confidence intervals (CI) were estimated. All analyses were stratified by the presence of liver metastases at baseline. We identified 3998 subjects from 31 Phase II-III oncology trials. The median age of the subjects was 61 (range, 18-90) years; 51% were male. The majority of subjects had locally advanced or metastatic disease; 29% had liver metastases at baseline. All studies included eligibility criteria related to liver function at baseline, with most requiring transaminases \#8804;2x ULN if liver metastases absent, \#8804;5x ULN if liver metastases present. The IR of new onset ALT elevations \#8805;3xULN was 5.9 per 1000 person-months (95% CI: 4.4, 7.8 per 1000 p-m) and 2.1 per 1000 person-months (95% CI: 0.8, 4.3 per 1000 p-m) for patients without and with liver metastases, respectively. No prevalent or incident cases of the combination endpoint occurred in patients with liver metastases. Among those without liver metastases, the prevalence of the combination endpoint at baseline was 0.04% (95% CI: 0%, 0.24%) and the IR of new cases during follow-up was 0.21 per 1000 person-months (95% CI: 0.01, 1.2 per 1000 p-m). Liver chemistry elevations were generally rare in this large cohort, which may be due in part to LFT-related enrolment criteria. The prevalence and incidence of liver chemistry elevations did not differ significantly by the presence of liver metastases, supporting uniform liver chemistry subject stopping criteria in oncology trials. These background rates are also useful benchmarks for assessing the clinical significance of liver enzyme elevations observed in future oncology clinical trials.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2142.