Faculty Collaboration Database

Phase I trial of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel: toxicity, pharmacokinetics, and activity. Mol Cancer Ther 2011 Jul;10(7):1300-7

Date

05/17/2011

Pubmed ID

21571911

DOI

10.1158/1535-7163.MCT-11-0259

Scopus ID

2-s2.0-79960119359 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Because liver involvement in patients with metastatic cancer has limited options and poor outcomes, we conducted a phase I study to determine the safety, activity, and pharmacokinetic characteristics of hepatic arterial infusion of nanoparticle albumin-bound paclitaxel (HAI nab-paclitaxel). Cohorts of three patients having predominant hepatic metastases received HAI nab-paclitaxel at three dose levels (180, 220, and 260 mg/m(2), respectively) infused for more than 1 hour every 3 weeks (3 + 3 design). Some patients participated in comparative pharmacokinetic studies (i.v. vs. HAI), receiving their first course i.v., to determine peak concentrations and effect of first-pass hepatic extraction compared with subsequent courses administered by HAI. The highest dose level was expanded to determine the safety and activity of HAI nab-paclitaxel. Thirty-eight patients were treated. There were no dose-limiting toxicities at doses up to 260 mg/m(2). Common adverse events included alopecia, fatigue, myelosuppresion, nausea, and vomiting. Three patients had stable disease for 4 or more months and 2 patients (1 of 12 with breast cancer and 1 of 1 with cervical cancer) achieved a partial response lasting for 5 and 15 months, respectively. Peak concentrations were lower (∼50%) with greater hepatic extraction of drug (∼42%) following HAI than i.v. infusion based on area under the curve comparison of drug exposure. HAI nab-paclitaxel showed partial hepatic extraction. At doses 260 mg/m(2) or less given for 1 hour every 3 weeks, the treatment was well-tolerated and showed activity in advanced cancer patients with predominant liver metastases.

Author List

Fu S, Naing A, Moulder SL, Culotta KS, Madoff DC, Ng CS, Madden TL, Falchook GS, Hong DS, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Albumins
Antineoplastic Agents
Female
Humans
Infusions, Intra-Arterial
Liver Neoplasms
Male
Middle Aged
Paclitaxel
Radiography
Treatment Outcome