Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies

David W. Nyman, Kimberley J. Campbell, Evan M Hersh, Kristen Long, Kelly Richardson, Vuong Trieu, Neil Desai, Michael J. Hawkins, Daniel D. Von Hoff

Research output: Contribution to journalArticle

215 Citations (Scopus)

Abstract

Purpose: ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007. Patients and Methods: Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m 2 as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle). Results: Thirty-nine patients were treated with an average of five cycles of ABI-007; 33% of patients received a six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m2, respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation. Conclusion: This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.

Original languageEnglish (US)
Pages (from-to)7785-7793
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number31
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Paclitaxel
Nanoparticles
Pharmacokinetics
Castor Oil
Neoplasms
Albumins
Albumin Receptors
Maximum Tolerated Dose
Premedication
Cell Surface Receptors
Peripheral Nervous System Diseases
Albumin-Bound Paclitaxel
Neutropenia
Intravenous Infusions
Ovarian Neoplasms
Area Under Curve
Cysteine
Lung Neoplasms
Carrier Proteins
Endothelial Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. / Nyman, David W.; Campbell, Kimberley J.; Hersh, Evan M; Long, Kristen; Richardson, Kelly; Trieu, Vuong; Desai, Neil; Hawkins, Michael J.; Von Hoff, Daniel D.

In: Journal of Clinical Oncology, Vol. 23, No. 31, 2005, p. 7785-7793.

Research output: Contribution to journalArticle

Nyman, David W. ; Campbell, Kimberley J. ; Hersh, Evan M ; Long, Kristen ; Richardson, Kelly ; Trieu, Vuong ; Desai, Neil ; Hawkins, Michael J. ; Von Hoff, Daniel D. / Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 31. pp. 7785-7793.
@article{b67a9179aff346b8b12ab4f99585f69f,
title = "Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies",
abstract = "Purpose: ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007. Patients and Methods: Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m 2 as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle). Results: Thirty-nine patients were treated with an average of five cycles of ABI-007; 33{\%} of patients received a six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m2, respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation. Conclusion: This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.",
author = "Nyman, {David W.} and Campbell, {Kimberley J.} and Hersh, {Evan M} and Kristen Long and Kelly Richardson and Vuong Trieu and Neil Desai and Hawkins, {Michael J.} and {Von Hoff}, {Daniel D.}",
year = "2005",
doi = "10.1200/JCO.2004.00.6148",
language = "English (US)",
volume = "23",
pages = "7785--7793",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "31",

}

TY - JOUR

T1 - Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies

AU - Nyman, David W.

AU - Campbell, Kimberley J.

AU - Hersh, Evan M

AU - Long, Kristen

AU - Richardson, Kelly

AU - Trieu, Vuong

AU - Desai, Neil

AU - Hawkins, Michael J.

AU - Von Hoff, Daniel D.

PY - 2005

Y1 - 2005

N2 - Purpose: ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007. Patients and Methods: Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m 2 as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle). Results: Thirty-nine patients were treated with an average of five cycles of ABI-007; 33% of patients received a six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m2, respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation. Conclusion: This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.

AB - Purpose: ABI-007 is a novel solvent-free, albumin-bound, 130-nm particle formulation of paclitaxel designed to avoid solvent-related toxicities and to deliver paclitaxel to tumors via molecular pathways involving an endothelial cell-surface albumin receptor (gp60) and an albumin-binding protein expressed by tumor cells and secreted into the tumor interstitium (secreted protein acid rich in cysteine). This study determined the maximum-tolerated dose (MTD) of ABI-007 monotherapy administered weekly (three weekly doses, repeated every 4 weeks) and assessed the pharmacokinetics of paclitaxel administered as ABI-007. Patients and Methods: Patients with advanced nonhematologic malignancies received ABI-007 without premedication at dose levels from 80 to 200 mg/m 2 as a 30-minute intravenous infusion once a week for 3 weeks, followed by 1 week of rest (one cycle). Results: Thirty-nine patients were treated with an average of five cycles of ABI-007; 33% of patients received a six cycles of treatment. MTDs for heavily and lightly pretreated patients were 100 and 150 mg/m2, respectively; and the dose-limiting toxicities were grade 4 neutropenia and grade 3 peripheral neuropathy, respectively. Maximum paclitaxel concentration and area under the curve increased linearly with dose. Dose-dependent changes in plasma clearance did not occur. Partial responses were observed in five patients with breast, lung, and ovarian cancers, all of whom had previously been treated with paclitaxel containing polyoxyethylated castor oil in the formulation. Conclusion: This study demonstrated that weekly ABI-007 can be administered at doses exceeding those typically used for paclitaxel containing polyoxyethylated castor oil. Pharmacokinetics were linear over the dose range studied. Antitumor responses occurred in patients previously treated with paclitaxel containing polyoxyethylated castor oil.

UR - http://www.scopus.com/inward/record.url?scp=32944481043&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32944481043&partnerID=8YFLogxK

U2 - 10.1200/JCO.2004.00.6148

DO - 10.1200/JCO.2004.00.6148

M3 - Article

C2 - 16258082

AN - SCOPUS:32944481043

VL - 23

SP - 7785

EP - 7793

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 31

ER -