This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nyman, D. W. Articles by Von Hoff, D. D. Search for Related Content PubMed PubMed Citation Articles by Nyman, D. W. Articles by Von Hoff, D. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Cancer Hazardous Substances DB TAXOL Related Articles Related Editorial Social Bookmarking                            What's this?

Phase I and Pharmacokinetics Trial of ABI-007, a Novel Nanoparticle Formulation of Paclitaxel in Patients With Advanced Nonhematologic Malignancies

From the Departments of Pharmacology/Toxicology and Medicine, Division of Hematology/Oncology, Arizona Cancer Center/University of Arizona Health Sciences Center, Tucson; Translational Genomics Research Institute, Phoenix, AZ; and American BioScience, Inc, Santa Monica, CA.

Address reprint requests to Daniel D. Von Hoff, MD, FACP, Translational Drug Development Division, Translational Genomics Research Institute, 445 N Fifth St, Suite 600, Phoenix, AZ 85004; e-mail: dvh{at}tgen.org

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/m² 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 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.

Supported by American BioScience, Inc, Santa Monica, CA.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004; and the 94th Annual Meeting of the American Association of Cancer Research, Washington, DC, July 11-14, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Paclitaxel Repackaged in an Albumin-Stabilized Nanoparticle: Handy or Just a Dandy?
  Alex Sparreboom, Sharyn D. Baker, and Jaap Verweij
  JCO 2005 23: 7765-7767 [Full Text]

This article has been cited by other articles:

				A. J. Chien, J. A. Illi, A. H. Ko, W. M. Korn, L. Fong, L.-m. Chen, M. Kashani-Sabet, C. J. Ryan, J. E. Rosenberg, S. Dubey, et al. A Phase I Study of a 2-Day Lapatinib Chemosensitization Pulse Preceding Nanoparticle Albumin-Bound Paclitaxel for Advanced Solid Malignancies Clin. Cancer Res., September 1, 2009; 15(17): 5569 - 5575. [Abstract] [Full Text] [PDF]

				W. J. Gradishar, D. Krasnojon, S. Cheporov, A. N. Makhson, G. M. Manikhas, A. Clawson, and P. Bhar Significantly Longer Progression-Free Survival With nab-Paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer J. Clin. Oncol., August 1, 2009; 27(22): 3611 - 3619. [Abstract] [Full Text] [PDF]

				G. Sonpavde, A. A. Elfiky, and J. E. Rosenberg Review: Novel agents for advanced bladder cancer Therapeutic Advances in Medical Oncology, July 1, 2009; 1(1): 37 - 50. [Abstract] [PDF]

				P. G. Morris and M. N. Fornier Microtubule Active Agents: Beyond the Taxane Frontier Clin. Cancer Res., November 15, 2008; 14(22): 7167 - 7172. [Abstract] [Full Text] [PDF]

				K. Cho, X. Wang, S. Nie, Z. Chen, and D. M. Shin Therapeutic Nanoparticles for Drug Delivery in Cancer Clin. Cancer Res., March 1, 2008; 14(5): 1310 - 1316. [Abstract] [Full Text] [PDF]

				N. A. Rizvi, G. J. Riely, C. G. Azzoli, V. A. Miller, K. K. Ng, J. Fiore, G. Chia, M. Brower, R. Heelan, M. J. Hawkins, et al. Phase I/II Trial of Weekly Intravenous 130-nm Albumin-Bound Paclitaxel As Initial Chemotherapy in Patients With Stage IV Non-Small-Cell Lung Cancer J. Clin. Oncol., February 1, 2008; 26(4): 639 - 643. [Abstract] [Full Text] [PDF]

				D. Mahadevan and D. D. Von Hoff Tumor-stroma interactions in pancreatic ductal adenocarcinoma Mol. Cancer Ther., April 1, 2007; 6(4): 1186 - 1197. [Abstract] [Full Text] [PDF]

				N. Wiedenmann, D. Valdecanas, N. Hunter, S. Hyde, T. A. Buchholz, L. Milas, and K. A. Mason 130-nm Albumin-Bound Paclitaxel Enhances Tumor Radiocurability and Therapeutic Gain Clin. Cancer Res., March 15, 2007; 13(6): 1868 - 1874. [Abstract] [Full Text] [PDF]

				S. S.W. Ng, A. Sparreboom, Y. Shaked, C. Lee, S. Man, N. Desai, P. Soon-Shiong, W. D. Figg, and R. S. Kerbel Influence of Formulation Vehicle on Metronomic Taxane Chemotherapy: Albumin-Bound versus Cremophor EL-Based Paclitaxel. Clin. Cancer Res., July 15, 2006; 12(14): 4331 - 4338. [Abstract] [Full Text] [PDF]

				J. J. Lee and S. M. Swain Peripheral Neuropathy Induced by Microtubule-Stabilizing Agents J. Clin. Oncol., April 1, 2006; 24(10): 1633 - 1642. [Abstract] [Full Text] [PDF]

				A. Sparreboom, S. D. Baker, and J. Verweij Paclitaxel Repackaged in an Albumin-Stabilized Nanoparticle: Handy or Just a Dandy? J. Clin. Oncol., November 1, 2005; 23(31): 7765 - 7767. [Full Text] [PDF]