Irinotecan in Cancer Patients with End-Stage Renal Failure

OBJECTIVE: To observe and report on the pharmacokinetics of Irinotecan in a patent with end-stage renal failure (ESRF) who was undergoing hemodialysis. CASE SUMMARY: A 64-year-old man with metastatic colorectal cancer who was on hemodialysis was treated with Irinotecan 50 mg/m(2) weekly for 3 weeks, followed by 1 week with no treatment. As the drug was well tolerated, the dosage was increased to 80 mg/m(2) after 2 cycles. Diagnostic testing of a hepatic lesion after 2 and 6 treatment cycles showed stable disease. The carcinoembryonic antigen value decreased to 40% of its pretreatment level. Pharmacokinetically, our patient had a lower apparent clearance and a higher maximum concentration of the active metabolite SN-38 (130 Uh/m(2), maximum concentration 0.4 mu g/L per mg of irinotecan) compared with published values from patients with normal renal function. Removal of irinotecan and Its metabolites by hemodialysis was negligible. DISCUSSION: The reason for the unexpectedly low clearance of SN-38 in our patient remains unclear. We speculate that inhibition of the OATP1B1 transporter by uremic toxins could be an explanation. Such a mechanism would explain excessive Irinotecan toxicity, as reported In previous case reports of patients undergoing hemodialysis. CONCLUSIONS: We conclude that approximately two-thirds of the standard weekly irinotecan dosage regimen should be considered in patients with ESRF