In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1302-1302
Abstract:
Purpose: We prospectively examined the effects of severe renal failure on the pharmacokinetics and toxicity of irinotecan. Experimental Design: The pharmacokinetics of irinotecan, SN-38 and SN-38 glucuronide (SN-38G), and irinotecan-induced toxicity in 3 cancer patients with severe renal failure (creatinine clearance [Ccr] ≤20 mL/min) who were undergoing dialysis and received 100 mg/m2 irinotecan as monotherapy were compared with those in 5 cancer patients with normal renal function (Ccr ≥60 mL/min). To ensure that the subjects had similar genetic backgrounds of UDP-glucuronosyltransferase (UGT) 1A1, patients with UGT1A1*1/*1, *1/*6, or *1/*28 were enrolled. Results: The estimated terminal elimination rate constant of SN-38 in patients undergoing dialysis was about one tenth that in patients with normal renal function (P=0.025). Consequently, the estimated t1/2 of SN-38 in patients with severe renal failure was roughly 10 times longer than that in patients without renal failure (P=0.025). About 50% of SN-38 was dialyzed with a 2.1-m2 dialysis membrane, whereas 27% was dialyzed with a 1.5-m2 membrane. All patients with severe renal failure experienced neutropenia (grade 2, 3 or 4 at nadir). In two of them experienced grade 2 or 3 neutropenia, the second irinotecan infusion was delayed 10 or 20 days by the prolonged neutropenia. Conclusions: Our results showed that the elimination of SN-38 was significantly delayed in patients with severe renal failure as compared with patients with normal renal function. We demonstrated SN-38 was partly dialyzed. The prolonged neutropenia was seen in patients with severe renal failure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1302. doi:10.1158/1538-7445.AM2011-1302
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-1302
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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