P1-23-2 - Predicting Febrile Neutropenia From Docetaxel(Dtx)-Based Therapy in a Population-Based Analysis of Solid Tumor Patients

Abstract

Background: Febrile neutropenia(FN) is a life-threatening complication of DTX therapy. It was reported that clearance of DTX associated with α1-acid glycoprotein, serum albumin level(ALB), CYP3A activity, liver dysfunction, and so on. This study aimed to identify predictive factors of DTX-induced FN.Methods: We investigated the incidence of FN in patients(pts) treated with DTX at the Osaka National Hospital from Apr 2008 to Oct 2013. The data obtained during the first 21 days were used for an analysis in the present study. We conducted to explore factor associated with FN by pts treated with DTX alone dose of 60mg/m2. Then we examined the validity of predictive factors in different doses and DTX-based combination therapy.Results: In total, 791 pts were included: 347 treated by monotherapy and 444 by combination therapy. Univariate analysis identified CYP3A inhibitor (≥moderate), PS (≥2), ALB, ALP and liver dysfunction (AST and/or ALT > 1.5xULN concomitant with ALP > 2.5xULN) as significant predictive factors; CYP3A inhibitor (≥moderate) and ALB was also an independent predictive factor in multivariable analysis at DTX alone dose of 60mg/m2. As the results of ROC analysis, optimal cut-off value of ALB associated with FN occurrence was determined to 3.2g/mL (AUC: 0.78). The incidence of FN was significantly higher in 63% of pts with ALB ≤3.2mg/dL compared with 11% of pts with ALB > 3.2mg/dL (OR:13.6, p < 0.0001). On the other hand, it was no difference in the incidence of FN in pts treated with DTX alone dose of ≤40mg/m2. Although combination therapy was similar to trend of monotherapy, the incidence of FN was frequent regardless of predictive factors in platinum-based triplet therapy.Conclusions: On the dose setting of DTX, it should be referring to ALB and combination of CYP3A inhibitors. Results of this study might suggest needs of dose reduction to ≤40mg/m2 in patients with ALB ≤3.2g/mL or combined with CYP3A moderate and strong inhibitors.