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.

Direct Inhibition and Down-regulation by Uremic Plasma Components of Hepatic Uptake Transporter for SN-38, an Active Metabolite of Irinotecan, in Humans

“…Total RNA was extracted by the miRNeasy Mini Kit (Qiagen), and cDNA was synthesized using oligo (dT) [12][13][14][15][16][17][18] primer, deoxynucleotide triphosphate mix, RT buffer and MultiScribe™ Reverse Transcriptase (Applied Biosystems, Foster City, CA).…”

Delayed Elimination of SN-38 in Cancer Patients with Severe Renal Failure

“…Studies examining the pharmacokinetics of irinotecan in renally impaired patients are scant. The pharmacokinetics of irinotecan in patients with mild renal impairment who had a creatinine clearance (Ccr) of 35 to 66 ml/min were similar to those in patients with normal renal function (de Jong et al, 2008). Although several case reports have examined the effects of more severe renal dysfunction requiring dialysis on the pharmacokinetics or toxicity of irinotecan (Venat-Bouvet et al, 2007;Czock et al, 2009), no prospective study has been performed; nevertheless, such rare patients are given irinotecan in clinical practice.…”

Irinotecan and its active metabolite, SN‐38: review of bioanalytical methods and recent update from clinical pharmacology perspectives

“…In particular, the association of grades 3 or 4 neutropenia tended to directly correlate with the individual's drop in creatinine clearance. For example in patients with creatinine clearance of 35-66 mL/min, almost 58% of the patients manifested grade 3 or 4 neutropenia in sharp contrast to patients with normal creatinine clearance (>130 mL/min), where only 14% of patients showed grade 3 or 4 neutropenia (de Jong et al, 2008). The data from this recently published study suggest that one has to pay attention to renal function, especially for irinotecan and other CPT analogs (de Jong et al, 2008).…”

“…In the study, clinical data from about 131 patients with standard recommended doses of irinotecan provided direct evidence of the association of renal function with both occurrence and gradation of hematological toxicity (i.e. neutropenia) (de Jong et al, 2008). In particular, the association of grades 3 or 4 neutropenia tended to directly correlate with the individual's drop in creatinine clearance.…”