Total bilirubin as a predictive marker for irinotecan-induced toxicity in patients with gastrointestinal cancer.

Abstract

68 Background: Irinotecan (CPT-11) is widely used for the treatment of patients with gastrointestinal cancer. However, CPT-11 can cause severe neutropenia and diarrhea.It has been reported that the AUC of SN-38, an active metabolite of CPT-11, correlated with Pre-treatment serum total bilirubin level (PTB), but there is no criteria of dose setting based on the PTB. Therefore, we retrospectively searched the PTB which can serve as an indicator for dose setting of CPT-11. Methods: We investigated the incidence of neutropenia and diarrhea at the first 28 days in patients with gastrointestinal cancer who were administered CPT-11 alone in Osaka National Hospital from June 2006 to July 2013. Correlation between PTB and grade 3-4 neutropenia or diarrhea were assessed. When toxicity of correlation exists, ROC (receiver operating characteristic) analysis was conducted to explore the cut-off value of the PTB. In addition, the incidence of febrile neutropenia (FN) in the cut-off value was compared. Results: 87 patients were analyzed. Of these, 65 were gastric cancer, 22 were colorectal cancer. Although PTB was significantly higher in patients who experienced grade 3-4 neutropenia than those who didn’t (p<0.001), PTB was not associated with grade 3-4 diarrhea. As the results of ROC analysis, cut-off value of PTB associated with grade 3-4 neutropenia was determined to 0.8 mg/dL. The incidence of FN was significantly higher in 20% of patients with PTB ≥ 0.8 mg/dL compared with 1.6% of patients with PTB < 0.8 mg/dL (OR: 15.5, p=0.01). On the other hand, in subgroup analysis showed no difference in the incidence of FN and neutropenia in patients whose dose was less than 100 mg/m². Conclusions: PTB was a predictive marker for CPT-11-induced severe neutropenia and FN. Results of this study suggested needs of dose reduction to less than 100 mg/m2 in patients with PTB ≥ 0.8mg/dL.