Irinotecan in Cancer Patients with End-Stage Renal Failure

Abstract

Objective:

To observe and report on the pharmacokinetics of irinotecan in a patient 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/m² weekly for 3 weeks, followed by 1 week with no treatment. As the drug was well tolerated, the dosage was increased to 80 mg/m² 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 L/h/m², maximum concentration 0.4 μg/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.