Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer

B. S. Adiwijaya; J. Kim; I. Lang; T. Csõszi; A. Cubillo; J. S. Chen; M. Wong; J. O. Park; J. S. Kim; K. M. Rau; B. Melichar; J. B. Gallego; J. Fitzgerald; B. Belanger; I. Molnar; W. W. Ma

doi:10.1002/cpt.720

Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer

B. S. Adiwijaya, J. Kim, I. Lang, T. Csõszi, A. Cubillo, J. S. Chen, M. Wong, J. O. Park, J. S. Kim, K. M. Rau, B. Melichar, J. B. Gallego, J. Fitzgerald, B. Belanger, I. Molnar, W. W. Ma

Medical Oncology

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t_1/2), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (C_max) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher C_avg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 C_max and diarrhea with tIRI C_max. Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m² (free-base; equivalent to 80 mg/m² salt base) Q2W over 100 mg/m² Q3W.

Original language	English (US)
Pages (from-to)	997-1005
Number of pages	9
Journal	Clinical pharmacology and therapeutics
Volume	102
Issue number	6
DOIs	https://doi.org/10.1002/cpt.720
State	Published - Dec 2017

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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10.1002/cpt.720

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Adiwijaya, B. S., Kim, J., Lang, I., Csõszi, T., Cubillo, A., Chen, J. S., Wong, M., Park, J. O., Kim, J. S., Rau, K. M., Melichar, B., Gallego, J. B., Fitzgerald, J., Belanger, B., Molnar, I., & Ma, W. W. (2017). Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer. Clinical pharmacology and therapeutics, 102(6), 997-1005. https://doi.org/10.1002/cpt.720

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title = "Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer",

abstract = "Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax. Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.",

author = "Adiwijaya, {B. S.} and J. Kim and I. Lang and T. Cs{\~o}szi and A. Cubillo and Chen, {J. S.} and M. Wong and Park, {J. O.} and Kim, {J. S.} and Rau, {K. M.} and B. Melichar and Gallego, {J. B.} and J. Fitzgerald and B. Belanger and I. Molnar and Ma, {W. W.}",

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year = "2017",

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doi = "10.1002/cpt.720",

language = "English (US)",

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AU - Adiwijaya, B. S.

AU - Kim, J.

AU - Lang, I.

AU - Csõszi, T.

AU - Cubillo, A.

AU - Chen, J. S.

AU - Wong, M.

AU - Park, J. O.

AU - Kim, J. S.

AU - Rau, K. M.

AU - Melichar, B.

AU - Gallego, J. B.

AU - Fitzgerald, J.

AU - Belanger, B.

AU - Molnar, I.

AU - Ma, W. W.

PY - 2017/12

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AB - Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax. Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.

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Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer

Abstract

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