title: Renal function as a predictor of irinotecan-induced neutropenia.
abstract: Although approximately half of the administered dose of irinotecan is recovered in urine, scarce data are available on the association of renal function with irinotecan pharmacokinetics and toxicity. Here, these relationships are investigated in 187 patients treated with irinotecan in a three-weekly schedule. No significant effects on irinotecan pharmacokinetics were found in these patients. However, in 131 patients treated with the registered dose, categorized renal function was related to hematological toxicity. The incidence of grade 3-4 neutropenia decreased as function of creatinine clearance, particularly in nonsmoking patients (P < 0.01). Patients with slower creatinine clearance (35-66 ml/min) had a four-times higher risk of grade 3-4 neutropenia (58% vs. 14%; P < 0.001). This study suggests that pretreatment renal function values are associated with irinotecan-induced neutropenia. A confirmatory analysis is warranted to determine whether measures of renal function should be incorporated in future attempts toward individualized treatment with irinotecan.
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center Rotterdam-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: de Jong
authors.forename: J M
authors.initials: JM
authors.lastname: van der Bol
authors.forename: R H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: T
authors.initials: T
authors.lastname: van Gelder
authors.forename: E A C
authors.initials: EA
authors.lastname: Wiemer
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003404:Creatinine / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D007668:Kidney / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009503:Neutropenia / Q000139:chemically induced* / Q000378:metabolism*; D011446:Prospective Studies; D012107:Research Design; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D003404:Creatinine; D004791:Enzyme Inhibitors; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme