Case Report
Gemcitabine-associated hemolytic-uremic syndrome*,**

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Abstract

Background: Gemcitabine has mild renal toxicity, but cases of gemcitabine-associated hemolytic-uremic syndrome (HUS) have been reported. Methods: A case is presented of a 45-year-old woman on prolonged gemcitabine treatment for ovarian cancer who developed HUS and recovered after drug discontinuation. A mini-review of the literature based on a MEDLINE search follows. Results: Including our own patient, a total of 26 cases of gemcitabine-associated HUS were identified. Median patient age was 52 years. Treatment was for various tumors at advanced stages, and in some patients, other anticancer drugs previously had been administered. Mean time between initiation of gemcitabine therapy and onset of HUS was 7.4 ± 3.5 months, or 21.9 ± 10.9 doses of gemcitabine. The calculated median cumulative dose of gemcitabine was 20,000 mg/m2 (range, 2,450 to 48,000 mg/m2, or a total of 70,000 mg). The onset of disease was noted up to 2 months after the last gemcitabine infusion. Diagnosis of HUS was confirmed histologically in 13 patients and based on clinical findings in the other 15. Treatment included drug discontinuation, steroids, fresh frozen plasma, hemodialysis, absorption chromatography, plasmapheresis, and various combinations thereof. Of 23 patients with reported outcome, 11 died within a few weeks. In two cases, death was believed to be a direct consequence of HUS. Reexposure to the drug was reported in three patients but was uncomplicated in only one. Conclusion: There are only a few confirmed cases of gemcitabine-associated HUS despite the widespread use of the drug. This potentially fatal complication is difficult to treat and should be widely known. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Case report

A 45-year-old woman was diagnosed with moderately differentiated adenocarcinoma of the ovary, FIGO IIIC stage, in November 1998. The patient underwent cytoreductive surgery with suboptimal resection. First-line chemotherapy with cisplatin/paclitaxel resulted in no tumor response. Second-line therapy with topotecan could not prevent radiologically documented tumor progression. After a short trial with tamoxifen, chemotherapy with carboplatin/paclitaxel was initiated, but the tumor progressed

Methods

A MEDLINE search up to December 31, 2001, was conducted to identify previous reports of gemcitabine-associated HUS. The search was done by intersecting gemcitabine with acute uremia, hemolysis, hemolytic-uremic syndrome, HUS, microangiopathic hemolytic anemia, (acute) renal failure, thrombocytopenia, and thrombotic microangiopathy. Identified articles were read carefully for references to other articles eventually not found by MEDLINE. Only cases meeting classic clinical or histologic criteria

Results

Including our own case and considering double and triple publications (one single case described by Brodowicz et al11 and Fung et al8; another case described by Casper et al,6 Flombaum et al,12 and Fung et al8; a third probably identical case reported by Lhotta et al13 and Fung et al8) a total of 26 different cases of HUS associated with gemcitabine were identified in the literature up to December 31, 2001.6, 8, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 Because of the varying

Discussion

Mechanisms of chemotherapy-induced renal dysfunction include prerenal perfusion deficits, damage to vessels or other structures of the kidneys, and HUS.26 HUS is a devastating, potentially fatal multisystem process characterized clinically by thrombocytopenia, microangiopathic hemolytic anemia, impaired renal function, and neurologic dysfunction and histologically by thrombotic microangiopathy.7 Its pathophysiology is incompletely understood, but endothelial injury is the central feature and

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    *

    Address reprint requests to Roland B. Walter, MD, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D2-373, Seattle, WA 98109-1024. E-mail: [email protected]

    **

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    Copyright © 2002 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.