Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors
PURPOSE: The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted.
METHODS: This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3.
RESULTS: Forty-five subjects were enrolled. No difference in dose-normalized AUC(0-last) for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected.
CONCLUSION: Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:65 |
|---|---|
| Enthalten in: |
Cancer chemotherapy and pharmacology - 65(2009), 1 vom: 30. Dez., Seite 97-105 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Denlinger, Crystal S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.10.2009 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00280-009-1008-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM188272054 |
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| 008 | 231223s2009 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00280-009-1008-7 |2 doi | |
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| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Denlinger, Crystal S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.10.2009 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted | ||
| 520 | |a METHODS: This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3 | ||
| 520 | |a RESULTS: Forty-five subjects were enrolled. No difference in dose-normalized AUC(0-last) for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected | ||
| 520 | |a CONCLUSION: Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Prodrugs |2 NLM | |
| 650 | 7 | |a Bevacizumab |2 NLM | |
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| 650 | 7 | |a Irinotecan |2 NLM | |
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| 700 | 1 | |a Blanchard, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Bernaards, Coen |e verfasserin |4 aut | |
| 700 | 1 | |a Litwin, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Spittle, Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Berg, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a McLaughlin, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Redlinger, Maryann |e verfasserin |4 aut | |
| 700 | 1 | |a Dorr, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Hambleton, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Holden, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Kearns, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Kenkare-Mitra, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Lum, Bert |e verfasserin |4 aut | |
| 700 | 1 | |a Meropol, Neal J |e verfasserin |4 aut | |
| 700 | 1 | |a O'Dwyer, Peter J |e verfasserin |4 aut | |
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