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Toxicity of irinotecan (CPT-11) and hepato-renal dysfunction

Ong, Simon YK1; Clarke, Stephen J1; Bishop, James1; Dodds, Helen M2; Rivory, Laurent P1,2

Case report
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Various clinical and laboratory parameters have been investigated for their ability to predict toxicity arising from the use of the anticancer drug, irinotecan (CPT-11). In particular, patients deficient in the conjugation of SN-38, a metabolite of CPT-11, are known to be at greater risk. We describe one case of a patient with metastatic colorectal cancer treated with a single dose of CPT-11 at 125 mg/m2. Although this patient lacked any known predictive factors for toxicity, he experienced severe side-effects several days later. We hypothesized that the toxicity in this patient was due to compromised SN-38 conjugation. Plasma samples were analyzed by reversed-phase high-performance liquid chromatography assay for CPT-11 and its metabolites at 96, 144, 168, 192 and 288 h post-administration. We observed that the concentrations of both the parent drug and its metabolites were markedly raised (11- to 60-fold expected). Additionally the estimated terminal half-lives were 1.5-7 times those expected (29.5, 101, 39.6 and 41.8 h for CPT-11, APC, SN-38G and SN-38, respectively). We conclude that the toxicity in this patient was not caused by deficient SN-38 conjugation, but by decreased drug excretion through both hepatic and renal routes.

1Medical Oncology, Sydney Cancer Centre, Missenden Road, Camperdown, NSW 2050, Australia. 2Department of Pharmacology, University of Sydney, NSW 2006, Australia.

Correspondence to LP Rivory, Medical Oncology, Sydney Cancer Centre, Missenden Road, Camperdown, NSW 2050, Australia. Tel: (+61) 2 9515 7376; Fax: (+61) 2 9519 1546; e-mail: lrivory@canc.rpa.cs.nsw.gov.au

(Received 19 April 2001; accepted 10 May 2001)

© 2001 Lippincott Williams & Wilkins, Inc.