Marrow: white blood cell count <3.0 × 109/L with neutrophils<1.5 × 109/L, platelet count<100×109/L and hemoglobin<90 g/L; Liver function: Total bilirubin >1.5 × upper limit of reference range; Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 × upper limit of reference range , or> 5 × upper reference range in subjects with liver metastasis; Renal function: Serum creatinine >1.5 × upper limit of reference range, or creatinine clearance<50 mL/min