Comparison of Child-Pugh (CP) criteria and NCI organ dysfunction working group (NCI-ODWG) criteria for hepatic dysfunction (HD): Implications for chemotherapy dosing

Abstract

6051 Background: Patients with HD may require drug dose modification based on the severity of HD. HD is often assessed using CP criteria, the use of which is advocated by the FDA. CP criteria, originally developed for patients with end-stage liver disease, has 5 components -total bilirubin (TB), albumin, prothrombin time, ascites & encephalopathy. NCI-ODWG sponsored trials have used different criteria which utilize two objective and readily measurable laboratory parameters specifically - TB & aspartate aminotransferase (AST). Comparison of these 2 criteria has not been done previously. Methods: Forty-five patients with varying degrees of HD were enrolled in a Phase I clinical trial of imatinib mesylate. Data to assess CP score were collected prospectively, along with AST. Patients were stratified into 4 groups as per the NCI-ODWG criteria based on TB & AST: normal [TB & AST ≤ upper limit of normal (ULN)], mild HD (TB > ULN to 1.5 x ULN or AST > ULN), moderate HD (TB >1.5–3 x ULN, any AST) & severe HD (TB >3 - 10 x ULN, any AST). After calculating the CP score for each patient, the 2 criteria were compared. Results: Conclusions: When assessed with a composite index of TB & AST (NCI-ODWG criteria), normal-to-mild HD correlated with CP group A (where dose modification of chemotherapeutic agents is usually not necessary). Moderate-to-severe HD assessed by TB & AST correlated with CP groups B & C (where dose modification may be necessary). The NCI-ODWG index, using TB & AST, provides a simple & objective way of assessing HD & can be applied in outpatient clinics & clinical trials for dose modification of chemotherapy. In cancer patients, TB is the predominant factor in classifying the severity of HD . (Support: 1UO1-CA099168–01 & NIH/NCCR/GCRC #5M01 RR 00056) No significant financial relationships to disclose.