Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization

Elliot B. Levy; Cody Peer; Tristan M. Sissung; Aradhana Venkatesan; Prakash Pandalai; Tim Greten; Marybeth S. Hughes; Charisse Garcia; Julie Peretti; William Figg; Andrew Lewis; Bradford Wood

doi:10.1016/j.jvir.2018.06.023

Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization

Elliot B. Levy, Cody Peer, Tristan M. Sissung, Aradhana Venkatesan, Prakash Pandalai, Tim Greten, Marybeth S. Hughes, Charisse Garcia, Julie Peretti, William Figg, Andrew Lewis, Bradford Wood

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Abstract

Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P =.16 and P =.05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P <.0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.

Original language	English (US)
Pages (from-to)	19-22
Number of pages	4
Journal	Journal of Vascular and Interventional Radiology
Volume	30
Issue number	1
DOIs	https://doi.org/10.1016/j.jvir.2018.06.023
State	Published - Jan 2019

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging
Cardiology and Cardiovascular Medicine

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Levy, E. B., Peer, C., Sissung, T. M., Venkatesan, A., Pandalai, P., Greten, T., Hughes, M. S., Garcia, C., Peretti, J., Figg, W., Lewis, A., & Wood, B. (2019). Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization. Journal of Vascular and Interventional Radiology, 30(1), 19-22. https://doi.org/10.1016/j.jvir.2018.06.023

Levy, EB, Peer, C, Sissung, TM, Venkatesan, A, Pandalai, P, Greten, T, Hughes, MS, Garcia, C, Peretti, J, Figg, W, Lewis, A & Wood, B 2019, 'Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization', Journal of Vascular and Interventional Radiology, vol. 30, no. 1, pp. 19-22. https://doi.org/10.1016/j.jvir.2018.06.023

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title = "Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization",

abstract = "Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P =.16 and P =.05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P <.0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.",

author = "Levy, {Elliot B.} and Cody Peer and Sissung, {Tristan M.} and Aradhana Venkatesan and Prakash Pandalai and Tim Greten and Hughes, {Marybeth S.} and Charisse Garcia and Julie Peretti and William Figg and Andrew Lewis and Bradford Wood",

note = "Funding Information: This study was supported by a Cooperative Research and Development agreement with BTG/Biocompatibles (B.W.), the Intramural Research Program of the National Institutes of Health and the Center of Interventional Oncology , Grant ZID BC011242-10 (B.W.). Publisher Copyright: {\textcopyright} 2018",

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doi = "10.1016/j.jvir.2018.06.023",

language = "English (US)",

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AU - Levy, Elliot B.

AU - Peer, Cody

AU - Sissung, Tristan M.

AU - Venkatesan, Aradhana

AU - Pandalai, Prakash

AU - Greten, Tim

AU - Hughes, Marybeth S.

AU - Garcia, Charisse

AU - Peretti, Julie

AU - Figg, William

AU - Lewis, Andrew

AU - Wood, Bradford

N1 - Funding Information: This study was supported by a Cooperative Research and Development agreement with BTG/Biocompatibles (B.W.), the Intramural Research Program of the National Institutes of Health and the Center of Interventional Oncology , Grant ZID BC011242-10 (B.W.). Publisher Copyright: © 2018

PY - 2019/1

Y1 - 2019/1

N2 - Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P =.16 and P =.05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P <.0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.

AB - Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P =.16 and P =.05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P <.0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.

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Pilot Study Comparing Systemic and Tissue Pharmacokinetics of Irinotecan and Metabolites after Hepatic Drug-Eluting Chemoembolization

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