QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Czock, D. Articles by Keller, F. Search for Related Content PubMed PubMed Citation Articles by Czock, D. Articles by Keller, F.

Irinotecan in Cancer Patients with End-Stage Renal Failure

Senior Physician, University Hospital Heidelberg, Heidelberg, Germany

Franz Maximilian Rasche, MD

Clinical Specialist, Medical Department I, Division of Nephrology, University Hospital Ulm, Ulm, Germany

Benjamin Boesler, MD

Clinical Specialist, Medical Department I, Division of Nephrology, University Hospital Ulm

Maria Shipkova, MD

Head of the Laboratory, Laboratory for Therapeutic Drug Monitoring and Clinical Toxicology, Central Institute of Clinical Chemistry and Laboratory Medicine, Stuttgart Hospital, Stuttgart, Germany

Frieder Keller, MD

Professor of Nephrology, Head of Division, Medical Department I, Division of Nephrology, University Hospital Ulm

Reprints: Dr. Czock, Universität Heidelberg, Medizinische Klinik (Krehl Klinik), Abteilung Innere Medizin VI, Klinische Pharmakologie, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. fax 49-6221-56-4642, david.czock{at}med.uni-heidelberg.de

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.

Key Words: colorectal cancer, hemodialysis, irinotecan (CPT-11), pharmacokinetics, SN-38

Published Online, January 27, 2009. www.theannals.com, DOI 10.1345/aph.1L511