Irinotecan in Cancer Patients with End-Stage Renal Failure

Czock, David; Rasche, Franz Maximilian; Boesler, Benjamin; Shipkova, Maria; Keller, Frieder

doi:10.1345/aph.1l511

Cited by 16 publications

(16 citation statements)

References 25 publications

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“…1D). In contrast, SN-38 was not dialyzable in previous studies (Venat-Bouvet et al, 2007;Czock et al, 2009), but they did not mention the specifications of the dialyzer used. There may be differences between the specifications of dialyzers used in this study and previous studies.…”

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confidence: 91%

Section: Introductionmentioning

confidence: 98%

“…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.Therefore, we prospectively examined the pharmacokinetics of irinotecan, SN-38, and SN-38G in cancer patients with severe renal failure who were undergoing dialysis compared with patients with normal renal function. We enrolled patients with UGT1A1*1/*1, *1/*6, or *1/*28 to ensure that the subjects had similar genetic backgrounds of UGT1A1.…”

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confidence: 98%

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

Fujita¹,

Sunakawa²,

Miwa³

et al. 2010

Drug Metab Dispos

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ABSTRACT:This prospective study is designed to examine the effects of severe renal failure on the pharmacokinetics of irinotecan. The pharmacokinetics of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G) in three cancer patients with severe renal failure [creatinine clearance (Ccr) <20 ml/min] who were undergoing dialysis and received 100 mg/m 2 irinotecan as monotherapy were prospectively compared with those in five cancer patients with normal renal function (Ccr >60 ml/min). To ensure that the subjects had similar genetic backgrounds of UDPglucuronosyltransferase (UGT) 1A1, patients with UGT1A1*1/*1, IntroductionSeveral lines of evidence have demonstrated that severe renal failure differentially affects drug uptake or efflux transporters and drug-metabolizing enzymes in the liver. Even drugs that are predominantly eliminated by hepatic transport and metabolism can be affected by severe renal failure, leading to unexpected consequences, such as atypical pharmacokinetics and an increased risk of adverse drug reactions. High levels of uremic toxins in such patients are partially implicated in these effects (Nolin et al., 2008).Irinotecan is extensively metabolized in the liver to an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by carboxylesterase, which is then conjugated predominantly by liver UDPglucuronosyltransferase (UGT) 1A1 to form inactive SN-38 glucuronide (SN-38G) (chemical structures; http://www.pharmgkb.org/ search/pathway/irinotecan/metabolites.html). Polymorphisms in UGT1A1 gene, such as UGT1A1*28 and *6, can cause reduced glucuronidation of SN-38, thus resulting in severe irinotecaninduced toxicity. UGT1A1*6/*6, *28/*28, and *6/*28 genotypes have been linked to significantly decreased conversion of SN-38 to SN-38G and severe neutropenia in Asians (Minami et al., 2007).Transporters expressed in the liver are also implicated in the pharmacokinetics of irinotecan and its metabolites. The uptake of SN-38 from the systemic circulation by hepatocytes is mediated by organic anion transporter peptide 1B1 (OATP1B1) (Nozawa et al., 2005). ATP-binding cassette transporters such as ABCC2, ABCB1, and ABCG2 govern the biliary excretion of irinotecan and its metabolites (http://www.pharmgkb.org/do/serve?objId ϭ PA2001&objCls ϭ Pathway).Because irinotecan is extensively metabolized and transported in the liver, attention has been focused on the hepatic factors underlying interpatient variability in pharmacokinetics of irinotecan. 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 per...

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confidence: 91%

Section: Introductionmentioning

confidence: 98%

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confidence: 98%

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

Fujita¹,

Sunakawa²,

Miwa³

et al. 2010

Drug Metab Dispos

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“…Both reports mention that by increasing the dose, prohibitive diarrhea was the consequence. 8,11 The worst outcome in higher irinotecan doses (above 125 mg/m²) was demonstrated in two other dialysis patients, where these dosages led to extreme GI toxicities and even death. 9 It can be concluded that irinotecan in terminal renal insufficiency should not be given at a dose above 50 mg/m².…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Only case reports on the pharmacology of irinotecan in patients with colon or rectal cancer are available at present. [7][8][9][10][11] We present the first case of combination chemotherapy in metastatic gastroesophageal cancer in a dialysis patient.…”

Section: Introductionmentioning

confidence: 99%

Complete response of a metastatic gastroesophageal adenocarcinoma on irinotecan-based chemotherapy in a dialysis patient

Geurs¹,

BULTE²

2010

IJNRD

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We present the first case report of a complete response of metastatic gastroesophageal cancer in a chronic hemodialysis patient with irinotecan-based chemotherapy. An elderly dialysis patient presented with diffuse liver metastases by a gastroesophageal adenocarcinoma. He received combination chemotherapy with 5 fluorouracil and irinotecan. After six months of chemotherapy, liver scans show complete remission. The principles, practice, and experience of chemotherapy with irinotecan during dialysis are discussed.

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Irinotecan and temozolomide for treatment of neuroblastoma in a patient with renal failure on hemodialysis

Armstrong

Dargart

Reichek

et al. 2013

Pediatric Blood & Cancer

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Renal failure is a rare complication of neuroblastoma or its therapy. To our knowledge, no reports describe treatment of children with neuroblastoma with chemotherapy in the setting of renal failure and maintenance hemodialysis. We report a 6-year-old child with high-risk neuroblastoma who developed renal failure requiring long-term hemodialysis. She was subsequently treated with 13 cycles of intravenous irinotecan 20 mg/m(2)/day and oral temozolomide 100 mg/m(2)/day for 5 days before disease progression without any dose adjustments, transfusions, febrile neutropenia or diarrhea. This case demonstrates that irinotecan and temozolomide can be safely administered in children with renal failure requiring hemodialysis.

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Irinotecan in Cancer Patients with End-Stage Renal Failure

Abstract: We conclude that approximately two-thirds of the standard weekly irinotecan dosage regimen should be considered in patients with ESRF.

Cited by 16 publications

References 25 publications

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

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

Complete response of a metastatic gastroesophageal adenocarcinoma on irinotecan-based chemotherapy in a dialysis patient

Irinotecan and temozolomide for treatment of neuroblastoma in a patient with renal failure on hemodialysis

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