Abstract
Bone-marrow suppression, especially leukopenia, neutropenia or thrombopenia is a dose limiting factor of gemcitabine (GEM). It was previously reported that the rate of GEM excreted in the urine was only 5％. However, it is unknown whether renal dysfunction influenced hematotoxicity. No dose recommendations exist for patients with renal dysfunction. Therefore, we investigated the correlation between moderate renal dysfunction and GEM-induced bonemarrow suppression. Fifty-five patients were analyzed retrospectively. Renal function was estimated from creatinine clearance (CLcr) calculated by the Cockroft-Gault formula. We defined CLcr ≦ 50 mL/min as moderate renal dysfunction. In the standard GEM therapy, GEM 1000 mg/m2 was administered intravenously on days 1, 8, and 15 every 4 weeks. However, patients with renal dysfunction often could not continue as scheduled the chemotherapy with GEM due to severe neutropenia. On day 15, the incidence of Grade 3 or 4 neutropenia in the renal dysfunction patients was significantly higher than that in the normal renal function patients (66.6％ vs 22.8％, P = 0.0194). Neutrophil counts on day 15 had a positive correlation with CLcr (R2 = 0.152, P < 0.01). In conclusion, we found that GEM-induced severe neutropenia was caused more frequently in renal dysfunction patients than normal renal function patients. These results indicate that patients with moderate renal dysfunction need an appropriate dose determined respectively when GEM is administered especially in the first course.
