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A Phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer

Published online by Cambridge University Press:  10 May 2018

Jacob Ezra Shabason ,
Jerry Chen ,
Smith Apisarnthanarax ,
Nevena Damjanov ,
Bruce Giantonio ,
Arturo Loaiza-Bonilla ,
Peter O’Dwyer ,
Mark O’Hara ,
Kim Reiss  and
Ursina Teitelbaum
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Jacob Ezra Shabason
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Jerry Chen
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Smith Apisarnthanarax
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Nevena Damjanov
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Bruce Giantonio
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Arturo Loaiza-Bonilla
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Peter O’Dwyer
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Mark O’Hara
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Kim Reiss
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Ursina Teitelbaum
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Paul Wissel
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Jeffery Drebin
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Charles Vollmer
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Michael Kochman
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Rosemarie Mick
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Norge Vergara
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Nirag Jhala
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Abigail Berman
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Jay Dorsey
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Sydney M. Evans
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Gary Kao
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
John N. Lukens
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
John P. Plastaras
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
James M. Metz
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
Edgar Ben-Josef
Affiliation:
University of Pennsylvania, Philadelphia, PA, USA
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Abstract

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OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

Type
Clinical Trial
Information
Journal of Clinical and Translational Science , Volume 1 , Supplement S1 , September 2017 , pp. 32 - 33
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Association for Clinical and Translational Science 2018