Concurrence of UGT1A polymorphism and end-stage renal disease leads to severe toxicities of irinotecan in a patient with metastatic colon cancer.

摘要: AIMS AND BACKGROUND Colorectal cancer is one of the most common malignancies in world, and irinotecan (CPT-11) useful its treatment. However, safety pharmacokinetics dialysis patients with metastatic colorectal are unclear. CASE REPORT We report case a 74-year-old man receiving chronic hemodialysis who had cancer. Palliative chemotherapy (80 mg/m2 weekly) was administered after hemodialysis. Blood samples were collected before 1.5, 3, 6, 9, 15 hours administration irinotecan. The peak serum concentrations (Cmax) SN-38 this patient 1,480 17.8 ng/mL, respectively, which similar to reported values normal renal function dose (75 mg/m2). area under concentration-time curve (AUC0-∞) 8,240 ng×h/mL for 619 SN-38. AUC0-∞ markedly higher than that function. Sequencing analysis UGT1A genes found variant alleles UGT1A1*28, UGT1A1*60 UGT1A9*22, may lead decreased glucuronidation excretion SN-38, account increased irinotecan-related toxicity. developed febrile grade 4 neutropenia on day 7 died septic shock 14. CONCLUSIONS polymorphisms failure accumulation have played role death patient. Irinotecan should be used cautiously screening help identifying lower rates greater susceptibility irinotecan-induced