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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2010

01-04-2010 | Translational Research and Biomarkers

Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films

Authors: Rong Liu, MD, PhD, Jesse B. Wolinsky, PhD, Joseph Walpole, BS, Emily Southard, MS, Lucian R. Chirieac, MD, Mark W. Grinstaff, PhD, Yolonda L. Colson, MD, PhD

Published in: Annals of Surgical Oncology | Issue 4/2010

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Abstract

Aim

To evaluate the efficacy of a polymer film designed for prolonged paclitaxel release at surgical margins to prevent local recurrence in non-small-cell lung cancer (NSCLC) following complete surgical resection in a murine model.

Methods

Poly(glycerol monostearate co-ε-caprolactone) polymer films were prepared with or without 10% (w/w) paclitaxel and characterized for prolonged tumor cytotoxicity in vitro against several NSCLC cell lines including LLC, NCI-H460, and NCI-H292. Films were implanted following complete LLC tumor resection and assessed in vivo for prevention of local tumor recurrence, impact on wound healing, and extent of local drug delivery. Plasma and local tissue concentrations of paclitaxel were compared following systemic administration and film implantation.

Results

The flexible polymeric films eluted paclitaxel over several weeks and remained cytotoxic to LLC, NCI-H460, and NCI-H292 cells in vitro for 50 days, while unloaded films did not impair tumor cell growth. Implanted paclitaxel films prevented local tumor recurrence in vivo in 83.3% of animals, compared with unloaded films (12.5%), systemic (22.2%) or locally administered paclitaxel (0%) (P < 0.005). Although minimal paclitaxel remained in either plasma or tissue 10 days after systemic injection, local paclitaxel concentration at the site of surgical resection was significantly greater (3,000-fold) at 10 days when paclitaxel was locally delivered via films (P = 0.024).

Conclusions

Local application of paclitaxel-loaded polymer films following surgical resection can prevent local tumor recurrence without impairing wound healing.
Appendix
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Metadata
Title
Prevention of Local Tumor Recurrence Following Surgery Using Low-Dose Chemotherapeutic Polymer Films
Authors
Rong Liu, MD, PhD
Jesse B. Wolinsky, PhD
Joseph Walpole, BS
Emily Southard, MS
Lucian R. Chirieac, MD
Mark W. Grinstaff, PhD
Yolonda L. Colson, MD, PhD
Publication date
01-04-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 4/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0856-z

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