Irinotecan in cancer patients with end-stage renal failure.
OBJECTIVE
To observe and report on the pharmacokinetics of irinotecan in a patient with end-stage renal failure (ESRF) who was undergoing hemodialysis.


METHODS
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 L/h/m(2), maximum concentration 0.4 microg/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.


CONCLUSIONS
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.
Czock
David
D
University Hospital Heidelberg, Heidelberg, Germany. david.czock@med.uni-heidelberg.de
Rasche
Franz Maximilian
FM
Boesler
Benjamin
B
Shipkova
Maria
M
Keller
Frieder
F
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy*; D005965:Glucuronates / Q000493:pharmacokinetics*; D006801:Humans; D000077146:Irinotecan; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D006435:Renal Dialysis
C114685:7-ethyl-10-hydroxycamptothecin beta-glucuronide; D000972:Antineoplastic Agents, Phytogenic; D005965:Glucuronates; D000077146:Irinotecan; D002166:Camptothecin